A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that middle schoolers from a predominantly Latinx community, with elevated levels of mental health problems, showed a reduction in symptoms during the early stages of the pandemic.

While the negative impact of the COVID pandemic on mental health is widespread, our study found that COVID-19 stay-at-home measures may have offered some protective effects for youth mental health early in the pandemic. These may be related to increased time with family, fewer social and academic pressures, more flexible routines, factors related to Latinx culture and the socio-emotional learning program that students were engaged in throughout the study period.”

Francesca Penner, MA, Study Coordinator, University of Mississippi Medical Center, Mississippi, MA, USA

The findings are based on the Identity Development in Typical Adolescents Study, a US-based ongoing longitudinal project tracking identity development in adolescence, that began in January 2020, prior to the onset of the pandemic.

A sample of 322 young adolescents (Mage = 11.99, 55% female), with a racial/ethnic composition of 72.7% Hispanic/Latinx; 9.3% Black or African American; 5.9% Multiple Races; 5.0% Asian; 1.6% White; and 1.2% American Indian, completed a mental health screening measure prior to the COVID-19 pandemic and at three bi-weekly time points starting one month into stay-at-home orders (mid-April, early May, late May, 2020). A subsample also completed a survey about their experience at home during COVID-19.

For youth who had elevated levels of mental health problems pre-pandemic, symptoms were significantly reduced across domains during the pandemic. Reductions in internalizing, externalizing and overall problems were clinically significant. For youth without notable pre-pandemic mental health problems, there were statistically significant reductions in internalizing and overall problems, and no change in attention or externalizing problems. Further analyses revealed that better family functioning was consistently related to lower mental health symptoms in youth during the bi-weekly follow-ups.

“These results have important clinical implications,” said senior author Carla Sharp, PhD, who led the study, and is a professor in the Department of Psychology, University of Houston, Texas. “First, promoting family functioning during COVID-19 may have helped protect or improve youth mental health during the pandemic. Further, it is important to consider cultural factors, such as familism and collectivism in Latinx communities that may buffer the early effects of disasters on mental health to COVID-19 stress.

“It also points to the need to determine specific features of stay-at-home measures that may be protective for youth mental health: for example ongoing socio-emotional learning programs in schools that can pivot to support mental health during crises, increased family time, changes in school structure, addressing middle school peer stress, more sleep, and more flexible routines.”

It is of course possible that the negative impact of stay-at-home orders began to take effect after the study period ended in May 2020. Assessments were completed while the academic year was still in session and the COVID-19 outbreak worsened in the school’s region after that time. Mental health may have declined later as the spread increased in the area or as stay-at-home measures continued.

The window when this study was conducted may present a unique “natural experiment” with the combination of increased time at home while stress related to COVID-19 in this region was not yet at its peak. Related, families who were financially impacted by COVID-19 may have had worsening stress that had not yet manifested during follow-up points. Further analysis indicated that in families where job loss occurred due to the pandemic, children did not experience the same level of reduction in total mental health problems at the first follow-up, compared to children in families where no job loss occurred.

“Our findings underline the importance of the family environment and Latinx collectivist values of community connection for promoting child resilience and brings into stark focus the possibility that school environments may exacerbate mental health difficulties,” said co-author, Jessica Hernandez Ortiz, a graduate student working with Dr. Sharp, who is currently leading the follow-up of the sample to assess more long-term effects of COVID-19 on adolescent mental health outcomes. “Removal from that context into a less pressured environment immediately and positively impacts mental health.”

The post Stay-at-home measures may have offered protective effects for youth mental health early in the pandemic appeared first on Parenting Boss.

Governments and health leaders across the globe are today calling for urgent action on adolescent wellbeing.

In an open letter published by The BMJ, they warn that the current generation of adolescents – 1.2 billion people aged 10-19 worldwide – “are at risk of inheriting a world blighted by climate change and scarred by covid-19.”

The 30 signatories include the Partnership for Maternal, Newborn & Child Health, the World Health Organization, United Nations and its related agencies, youth led organizations, civil society, foundations, academia, and government representatives in Africa, the Americas, Asia and Europe.

Although adolescents have been spared the most severe direct effects of the pandemic, the indirect effects on their wellbeing are devastating, they argue.

They explain that, even before covid-19, adolescents and young adults faced many challenges to their wellbeing, including social injustice and inequalities, inadequate mental health, and a crisis of connection to family, community and society, with increasing numbers living on the streets or dropping out of school.

Yet between 2003 and 2015, development assistance for adolescent health accounted for only 1.6% of total development assistance for health, despite a third of the total global burden of disease estimated to have roots in adolescence.

When adolescents move into young adulthood, many face unemployment or unstable employment, they add. In 2017, 34% of young women and 10% of young men aged 15-24 years were not in employment, education or training, with more pronounced disparities in northern Africa and southern Asia.

And even among employed adolescents and young adults, an increasing proportion have poor job security, variable weekly earnings, and minimal or no health or social security coverage.

“These examples show that, as a global community, we have paid insufficient attention to the multidimensional and intersectional nature of adolescent wellbeing and the importance of the transition to young adulthood,” they write.

As a result, they have committed to a call to action for adolescent wellbeing to ensure that today’s adolescents are empowered to solve the problems they are inheriting.

Underpinning this is a new agreed definition and conceptual framework for adolescent wellbeing to inform policies and programming.

This framework includes good health and optimum nutrition; connectedness, positive values, and contribution to society; safety and a supportive environment; learning, competence, education, skills, and employability; and agency and resilience.

“We invite everyone – decision makers, policy makers, civil society, service providers, educators, donors, innovators, and, most importantly, adolescents themselves – to support this call to action,” they write.

“Together, we can ensure that it results in concrete policies, integrated programs, and sustained investments for adolescent wellbeing.”

They stress that adolescents, youth and youth led organizations “are at the heart of this initiative and will continue to be so.” But they say “we all have a part to play in achieving these goals if we are to deliver a more equitable and inclusive world for this and future generations.”

The post Global health leaders call for urgent action to promote adolescent wellbeing appeared first on Parenting Boss.

In some cancers, including leukemia in children and adolescents, obesity can negatively affect survival outcomes. Obese young people with leukemia are 50% more likely to relapse after treatment than their lean counterparts.

Now, a study led by researchers at UCLA and Children’s Hospital Los Angeles has shown that a combination of modest dietary changes and exercise can dramatically improve survival outcomes for those with acute lymphoblastic leukemia, the most common childhood cancer.

The researchers found that patients who reduced their calorie intake by 10% or more and adopted a moderate exercise program immediately after their diagnosis had, on average, 70% less chance of having lingering leukemia cells after a month of chemotherapy than those not on the diet-and-exercise regimen.

Lingering cancer cells in the bone marrow, which are more likely to be found in overweight individuals, are associated with worse survival and a higher risk of relapse, often leading to more intense treatments like bone marrow transplants and immunotherapy.

We tested a very mild diet because this was our first time trying it, and the first month of treatment is already so difficult for patients and families. But even with these mild changes in diet and exercise, the intervention was extremely effective in reducing the chance of having detectable leukemia in the bone marrow.”

Dr. Steven Mittelman, Senior Author, Chief of Pediatric Endocrinology, UCLA Mattel Children’s Hospital and Member of the UCLA Jonsson Comprehensive Cancer Center

As part of the clinical trial, which took place at Children’s Hospital Los Angeles, researchers worked with registered dieticians and physical therapists to create personalized 28-day interventions for 40 young people between the ages of 10 and 21 who were newly diagnosed with acute lymphoblastic leukemia.

The intervention was designed to cut participants’ calorie intake by a minimum of 10% in order to reduce both fat gain and lean muscle loss. The physical activity component included a target level of 200 minutes per week of moderate exercise.

The results, published in the American Society of Hematology’s journal Blood Advances, showed a decrease in fat gain among those who were overweight and obese, as well as an improved insulin sensitivity and an increase in the beneficial hormone adiponectin, which is involved in regulating glucose and breaking down fatty acids. Most importantly, the researchers found a 70% decrease in the chance of having lingering leukemia cells in the bone marrow -; known medically as minimal residual disease -; when compared with a historical control group.

“We hoped the intervention would improve outcomes, but we had no idea it would be so effective,” Mittelman said. “We can’t really add more toxic chemotherapies to the intense initial treatment phase, but this is an intervention that likely has no negative side effects. In fact, we hope it may even reduce toxicities caused by chemotherapy.”

“This is the first trial to test a diet-and-exercise intervention to improve treatment outcomes from a childhood cancer,” said principal investigator and lead author Dr. Etan Orgel, Director of the Medical Supportive Care Service in the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles. “This is an exciting proof-of-concept, which may have great implications for other cancers as well.”

Next steps include further testing of the approach in a multicenter randomized trial, which will be launched later this year, the researchers said.

The post Modest dietary changes and exercise can improve survival outcomes for young people with leukemia appeared first on Parenting Boss.

A collaborative team centered in the University of California, Irvine (UCI) and including Children’s Hospital Orange County (CHOC) and Chapman University (CU) has been awarded a three-year grant totaling in excess of $2.3 million, to address the health impacts of adverse childhood experiences (ACEs) using precision medicine. Announced by the California Governor’s Office of Planning & Research, in partnership with the Office of the California Surgeon General, the award is part of the California Initiative to Advance Precision Medicine (CIAPM). The research project will begin May 2021.

Led by Tallie Z. Baram, MD, PhD, Bren Distinguished Professor and director of the Conte Center at UCI, the UCI, CHOC and CU team has established two goals. The first is to identify the degree to which unpredictability of early life experiences interacts with established ACEs to influence children’s neurodevelopment. The second is to employ a novel epigenetic approach, with a goal of discovering, for each child, a marker that can predict their level of resilience, so targeted interventions can be delivered to children who need them most.

The burden of ACEs is not equally distributed. There exists a greater risk of exposure among low socioeconomic and racial/ethnic minority communities. Through this project we seek to determine how both established ACEs and a new, preventable ACE influence children’s emotional and cognitive behaviors, and identify a way to predict early-on if a child is impacted by ACEs or is resilient. Our goal is to enable caregivers to provide special attention and intervention to those most at need, ameliorating health disparities.”

Tallie Z. Baram, MD, PhD, Bren Distinguished Professor and director of the Conte Center at UCI

ACEs affect two-thirds of Californians directly and can complicate physical and mental health across the lifespan. The UCI team intends to screen 100,000 children across Orange County, California for the study.

In addition to Baram, principal investigators on the UCI team include Michael Weiss, DO, FAAP, vice president of population health for Children’s Hospital Orange County (CHOC); Dan Cooper, MD, associate vice chancellor for clinical and translational science, professor of pediatrics and biomedical engineering, and director of UCI’s Institute for Clinical and Translational Research; Laura Glynn, PhD, professor of psychology, and associate dean for research at Chapman University; and, Candice Taylor-Lucas, MD, associate professor in the Department of Pediatrics and co-director for UCI’s Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC) program.

UCI was among four awardees announced by the California Governor’s Office of Planning and Research, in partnership with the Office of the California Surgeon General. The other three awards were given to Children’s Hospital Los Angeles, Loma Linda University and the University of California, San Francisco.

A total of $9 million in state funds were awarded to support the proof-of principle demonstration projects for families and communities with ACEs with an aim to improve access, care and outcomes through collaboration between academic, community, nonprofit and private partners.

“This State of California initiative recognizes that ACEs have profound cumulative negative impacts on mental and physical health of children, impacts that remain for a lifetime,” said Baram. “Along with the state, we believe precision medicine holds promise to more fully apply data to improve health and healthcare, and we intend to deliver on that promise.”

The post UCI-led team to address health impacts of adverse childhood experiences using precision medicine appeared first on Parenting Boss.

A team of researchers has sought to mitigate the mental health impacts of COVID-19 on adolescents by harnessing previous research on youth physical and mental health.

Their review also drew on the psychological stressors of the 2011 Great East Japan Earthquake and Tsunami on children. The results were published in the Tohoku Journal of Experimental Medicine on March 26, 2021.

We combined past research on the psychological stress on children with present studies on the effects of COVID-19. We found that exercise, even in limited forms, would help reduce mental health issues.”

Junko Okuyama, Department of Physical Medicine and Rehabilitation at Tohoku University Hospital and Study’s Lead Author

Lockdowns, school closures, and lack of opportunities for physical exercise have taken a huge toll on the mental wellbeing of children across the globe. This stress is likely to have a significant impact on their later development.

In Japan, activities were limited in the form of self-restraint rather than a stringent lockdown. Nevertheless, schools were closed temporarily from March until late May 2020 during the Japanese government’s first state of emergency.

Most studies on child adolescents in the COVID-19 pandemic have reported worsening psychological status and anxiety as a result of lockdown and decreased physical activity. But there is still no long term data on COVID-19’s influence on the mental health of young people.

The research group turned to the past for answers.

The Great East Japan Earthquake and subsequent Fukushima Daiichi disaster, like COVID-19, upended the lives of many. Okuyama’s prior research had examined the counseling for high school students who had suffered through the earthquake, finding that it was effective against PTSD and depression but not against anxiety.

This, along with other research, was drawn upon to argue that introducing physical activities is a simple and inexpensive way to provide mental health support.

“COVID-19 has posed a significant threat to our health both physically and mentally, and our youth are especially vulnerable to the latter,” added Okuyama. “By examining the relationship between physical activity and the psychological state of adolescents undergoing traumatic events, we were able to say sufficiently that physical activity improves their state of mind.”

Looking ahead, the research group are hoping to measure psychological test scores between physically active and non-physically active high school students.

The post Harnessing previous research to mitigate the mental health impacts of COVID-19 on adolescents appeared first on Parenting Boss.

A team of researchers at the University of Alberta has uncovered a long-sought link in the battle to control cholesterol and heart disease.

The protein that interferes with low-density lipoprotein (LDL) receptors that clear “bad” cholesterol from the blood was identified in findings recently published in Nature Communications by Dawei Zhang, associate professor of pediatrics in the Faculty of Medicine & Dentistry. Excess LDL cholesterol can lead to atherosclerosis–a narrowing and hardening of arteries–and ultimately, heart attack.

We have known for many years that these receptors could be cleaved, but nobody knew which protein was responsible. There had been several attempts around the world but nobody else was successful.”

Dawei Zhang, Associate Professor of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta

Now that the culprit has been identified, Zhang’s lab is already at work to find a drug to target the protein, allowing the receptors to clear more LDL.

A cholesterol-reducing class of drugs called statins–Lipitor and Crestor are two well-known brand names–has been shown to reduce cardiac events by 20 to 40 per cent, but they have side-effects that mean they can’t be given in high enough doses to work for everyone. The new drug would be used in combination with statins to boost their effect, Zhang said.

Zhang’s team stumbled upon the role of the protein–membrane type 1 matrix metalloproteinase–by accident while studying another protein involved in heart function. They then set out to repeat and confirm their findings in mouse, rat and human cells, working in collaboration with researchers in China and other faculty members at the U of A. Their study was funded by the Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research. Zhang is also a member of the Women and Children’s Health Research Institute.

The protein has other critical physiological functions, Zhang explained, so his lab will work to identify and focus on the specific region within the protein that acts on the LDL receptor. They are also working with a new technique to further target their potential drug so it will work only within the liver, further reducing the likelihood of unwanted side-effects. Their early results are encouraging, Zhang said.

Zhang noted the protein is also critical for cancer tumour invasion, so the team will collaborate with U of A oncology experts to learn more.

“The one protein is a shared risk factor for the two most common diseases in humans–cancer and cardiovascular disease,” he said. “We will explore whether we can target one protein to reduce the incidence of the two most common human diseases.”

The post Researchers identify protein that interferes with the body’s ability to get rid of ‘bad’ cholesterol appeared first on Parenting Boss.

Overweight children and adolescents receiving chemotherapy for treatment of leukemia are less successful battling the disease compared to their lean peers. Now, research conducted at the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles indicates that modest changes in diet and exercise can greatly increase survival in youth treated for acute lymphoblastic leukemia (ALL), the most common childhood cancer.

To our knowledge, this is the first study to show that by limiting calories and increasing exercise we can make chemotherapy more effective in eliminating leukemia cells within the first month of therapy, decreasing the chances of disease relapse in children and adolescents.”

Etan Orgel, MD, MS, Principal Investigator, Director of the Medical Supportive Care Service in the Cancer and Blood Disease Institute, Children’s Hospital Los Angeles

The study is published in the American Society of Hematology’s journal Blood Advances.

Youth who are obese when they begin chemotherapy are more than twice as likely to have remaining cancer cells after one month of treatment–and an increased chance of disease relapse–compared to their lean counterparts. To address this, the investigators worked with registered dietitians and physical therapists who created personalized diet and exercise plans for 40 patients between the ages of 10 and 21 with newly diagnosed leukemia.

The investigators found that patients who reduced their caloric intake by at least 10% and began a modest exercise regimen beginning at diagnosis were, on average, 70% less likely to have remaining leukemia cells in their bone marrow one month after beginning chemotherapy, compared to previously treated patients who did not participate in the diet and exercise intervention. Remaining leukemia cells, called minimal residual disease, is one of the strongest predictors of poor survival outcomes.

“This is proof of concept that it is possible to increase the effectiveness of chemotherapy without adding other medications and their potential side effects,” says Dr. Orgel, who is also an associate professor of clinical pediatrics at the Keck School of Medicine of USC. “This short-term intervention is inexpensive and easily available to providers and families everywhere.”

The investigators found that by limiting fat, patients also had decreased insulin resistance as well as increased levels of adiponectin, a metabolic hormone associated with glucose regulation. Identification of these potential biomarkers paves the way to using this intervention to impact other types of cancer.

“Changing diet and exercise made the chemotherapy work better– that’s the big news of this study. But we also need to figure out how,” says Steven Mittelman, MD, PhD, Chief of Pediatric Endocrinology at UCLA Mattel Children’s Hospital and member of UCLA’s Jonsson Comprehensive Cancer Center. “Understanding the biological changes responsible for this effect will help us make these interventions even better.” Dr. Mittelman co-led the study and was senior author on the paper.

This clinical trial, called Improving Diet and Exercise in ALL (IDEAL-1), builds on basic and preclinical research conducted for more than a decade at Children’s Hospital Los Angeles. This “bench-to-bedside and back” approach provides new insights for treating devastating diseases, like cancer. Physicians observe an unmet clinical need in their patients, collaborate with colleagues in the lab and can then deliver an intervention to the clinic to test its effectiveness.

A randomized trial is planned for later this year. Called IDEAL-2, the study will be conducted by Dr. Orgel and Dr. Mittelman through the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium, headquartered at Children’s Hospital Los Angeles under the medical leadership of Alan Wayne, MD, and Deepa Bhojwani, MD.

The post Changing diet and exercise can make chemotherapy more effective in youth with leukemia appeared first on Parenting Boss.

Children and young adults who receive CAR T-cell therapy for the most common childhood cancer – acute lymphoblastic leukemia – suffer remarkably fewer relapses and are far more likely to survive when the treatment is paired with a subsequent stem cell transplant, a new study finds.

The research, with an average follow up of nearly five years, suggests that stem cell transplants offer long-term benefits for young patients who receive the cutting-edge immunotherapy. CAR T-cell therapy results in complete remission in 60%-100% of patients initially, but the relapse rate is high. However, among those who received a stem cell transplant after CARs, the relapse rate was less than 10% two years later.

More than 50% of kids in other studies with a different CAR relapse, with the majority of them losing the target the CAR goes after. Most of these kids have a single shot at this life-saving and paradigm-changing therapy called CAR T-cells. We should do all we can to maximize the chance for a cure, and right now that means a transplant after CAR therapy for most.”

Daniel “Trey” Lee, MD, Researcher, Pediatric Oncologist and Director of Pediatric Stem Cell Transplant and Immunotherapy at UVA Children’s and the UVA Cancer Center

About CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy takes a person’s own immune cells and genetically modifies them to make them more effective cancer killers.

The approach has shown high remission rates – up to 100% – 28 days after it is given to children and young adults with B-cell acute lymphoblastic leukemia. But a significant number relapse, the limited data available suggests. One study found that more than 40% had relapsed 13.1 months later.

To determine if stem cell transplants could help, the new study looked at outcomes in 50 children and young adults, ages 4 to 30. The median age was 13.5 years.

Among the 21 who received an allogenic stem cell transplant after CARs, only 9.5% had relapsed 24 months later. In comparison, all of those who did not receive a stem-cell transplant had relapsed.

“Even as impactful as CAR T-cell therapy is for children with relapsed leukemia, we now know that the best outcomes happen when the child undergoes a stem cell transplant afterwards,” Lee said. “Many parents turn to CAR T-cells to possibly avoid a stem cell transplant, and that is entirely understandable. But there is a window of opportunity after CARs to cure more of these incurable kids with a transplant; our study demonstrates this.” His hope for the future is for the field to be able to distinguish up front those who need a transplant and those who do not.

UVA Children’s and the UVA Cancer Center offer several types of CAR T-cell therapies for both children and adults with leukemia and lymphoma.

Findings published

The researchers have published their findings in the Journal of Clinical Oncology. The research team consisted of Nirali N. Shah, Daniel W. Lee, Bonnie Yates, Constance M. Yuan, Haneen Shalabi, Staci Martin, Pamela L. Wolters, Seth M. Steinberg, Eva H. Baker, Cindy Delbrook, Maryalice Stetler-Stevenson, Terry J. Fry, David F. Stroncek and Crystal L. Mackall. Lee disclosed that he does consulting work for Harpoon Therapeutics and Juno Therapeutics and that UVA receives clinical trial support from Kite Pharma. A full list of disclosures is included in the paper.

The work was supported by the National Institutes of Health’s Intramural Research Program, National Cancer Institute (grant ZIA BC 011498) and NIH Clinical Center, and by a St. Baldrick’s/Stand Up 2 Cancer Pediatric Dream Team Translational Cancer Research Grant.

The post Stem cell transplants offer long-term benefits for pediatric cancer patients receiving immunotherapy appeared first on Parenting Boss.

New “sweat stickers” may streamline the early diagnosis of cystic fibrosis by enabling scientists to easily gather and analyze sweat from the skin of infants and children. The stickers matched the performance of previous, more cumbersome devices when tested with 51 subjects, suggesting the stickers could address design obstacles that have held back the diagnosis and treatment of cystic fibrosis in pediatric patients.

Diagnosing cystic fibrosis in infancy or childhood is critical to achieve good outcomes, as current treatments must be given early to extend lifespans and alter the course of the disease. Many current diagnostics work by detecting levels of chloride in sweat, which are elevated in cystic fibrosis patients. However, these tests must often be repeated and use unwieldy wrist-wrapped devices, making them impractical for infants with soft skin and low levels of sweat.

To address this need, Tyler Ray and colleagues developed their sweat stickers, which are soft microfluidic devices with a multilayered design that can conform to the skin of both infants and adults. The stickers rapidly collect and store sweat from the skin, which scientists can then analyze using a smartphone application. The stickers collected sweat as effectively as a traditional method named MSCS in a pilot study with 18 healthy subjects and 33 patients ranging from 2 months to 51 years old. Unlike MSCS, the stickers gathered enough sweat to avoid any repeated tests and did not cause uncomfortable skin indentations in infants.

The researchers call for larger studies to further establish their platform’s accuracy and precision.

The post New sweat stickers may streamline diagnosis, treatment of cystic fibrosis in in pediatric patients appeared first on Parenting Boss.

An investigational vaccine designed to protect against the B.1.351 SARS-CoV-2 variant has been administered as part of a new Phase 1 clinical trial evaluating the vaccine candidate’s safety and immunogenicity in adult volunteers. The vaccine, known as mRNA-1273.351, was developed by the biotechnology company ModernaTX, Inc., based in Cambridge, Massachusetts. The trial is led and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The trial will enroll approximately 210 healthy adult volunteers at four clinical research sites in the United States that are part of the NIAID-funded Infectious Diseases Clinical Research Consortium (IDCRC).

The B.1.351 SARS-CoV-2 variant, first identified in the Republic of South Africa, has been detected in at least nine states in the United States. Preliminary data show that the COVID-19 vaccines currently available in the United States should provide an adequate degree of protection against SARS-CoV-2 variants. However, out of an abundance of caution, NIAID has continued its partnership with Moderna to evaluate this variant vaccine candidate should there be a need for an updated vaccine.”

Anthony S. Fauci, M.D., NIAID Director

Investigators from NIAID and Moderna co-developed the mRNA-1273 vaccine, which is currently authorized by the Food and Drug Administration (FDA) for emergency use in the United States for the prevention of COVID-19 in adults 18 years of age and older. The vaccine is administered as two 100-microgram (mcg) doses 28 days apart. The vaccine uses lipid nanoparticles to deliver instructions to the body’s cells for making a stabilized version of the spike protein found on the surface of the SARS-CoV-2 virus. After the vaccination, the immune system detects the stabilized spike protein and begins building a response against the virus. The variant vaccine candidate developed by Moderna, mRNA-1273.351, differs from the currently-authorized Moderna vaccine in that it delivers instructions for making the SARS-CoV-2 spike that incorporates key mutations in the B.1.351 virus variant. In addition to the Phase 1 clinical trial, investigators at NIAID’s Vaccine Research Center are collaborating with Moderna to evaluate mRNA-1273.351 in animal models.

The trial will enroll people ages 18 years and older who already have received the mRNA-1273 vaccine, as well as people ages 18 through 55 years who have not received any COVID-19 vaccine. Approximately 60 volunteers who previously received mRNA-1273 as a participant in NIAID’s Phase 1 trial of mRNA-1273 (which began in March 2020) will enroll in the new variant Phase 1 trial. Approximately one year ago, these volunteers received two vaccinations of mRNA-1273 28 days apart at varying doses: 50 mcg, 100 mcg or 250 mcg. As part of the variant vaccine trial, these volunteers will be randomized to receive either a single booster vaccination of 50 mcg of mRNA-1273.351 (group 1A) or a single vaccination containing one 25-mcg dose of mRNA-1273 and one 25-mcg dose of mRNA-1273.351 (group 1B). The remaining participants from the March 2020 trial will be offered a booster shot of mRNA-1273 as part of a separate clinical trial protocol (for more information see clincialtrials.gov: NCT04283461).

The Phase 1 variant vaccine trial also will enroll approximately 150 volunteers ages 18 through 55 years who have not received any COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, and do not have health conditions that are associated with an increased risk of severe illness from SARS-CoV-2 infection, such as cancer, heart conditions, type 2 diabetes mellitus, severe obesity or chronic kidney disease. These volunteers will be randomly assigned to one of eight cohorts:

Group 2C (20 participants) will receive two vaccinations 28 days apart: 100 mcg mRNA-1273.351, followed by 100 mcg of mRNA-1273.351.

• Group 2A (15 participants) will receive three vaccinations 28 days apart: 100 mcg of mRNA-1273, followed by 100 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273.351.
• Group 2B (15 participants) will receive three vaccinations 28 days apart: 50 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273.351.
• Group 2D (20 participants) will receive two vaccinations 28 days apart: 50 mcg of mRNA-1273.351, followed by 50 mcg of mRNA-1273.351.
• Group 2E (20 participants) will receive two vaccinations 28 days apart: 100 mcg of mRNA-1273, followed by 100 mcg of mRNA-1273.351.
• Group 2F (20 participants) will receive two vaccinations 28 days apart: 50 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273.351.
• Group 2G (20 participants) will receive a single vaccination at their initial visit which combines 50 mcg of mRNA-1273 plus 50 mcg of mRNA-1273.351. Twenty-eight days later, they will receive another single vaccination of the same dose and combination.
• Group 2H (20 participants) will receive a single vaccination at their initial visit which combines 25 mcg of mRNA-1273 plus 25 mcg of mRNA-1273.351. Twenty-eight days later, they will receive another single vaccination of the same dose and combination.

The trial will evaluate the safety and reactogenicity of the vaccine candidate as well as its ability to induce an immune response. Reactogenicity can include injection site reactions like redness and pain as well as systemic reactions such as fever, headache, fatigue or muscle aches. Participants will be closely monitored for safety and will be asked to return to the study clinic for multiple follow-up visits between vaccinations and for additional visits during the year after their last vaccination. Participants also will be asked to provide blood samples at specified times throughout the trial. Scientists will use these samples to measure the immune response against circulating strains of SARS-CoV-2, including the B.1.351 variant.

An independent safety monitoring committee (SMC) will oversee the trial by regularly reviewing safety reports. The SMC can make a recommendation to the sponsor (NIAID) whether the trial should be halted, modified or terminated at any point.

The Phase 1 clinical trial will enroll participants at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle, Emory University in Atlanta, Vanderbilt University Medical Center (VUMC) in Nashville, and Cincinnati Children’s Hospital Medical Center (CCHMC) in Cincinnati. The trial is led by investigators Lisa A. Jackson, M.D., M.P.H., senior investigator at KPWHRI; Evan Anderson, M.D., professor of pediatrics and medicine at Emory; Nadine Rouphael, M.D., professor of medicine at Emory; C. Buddy Creech, M.D., M.P.H., director of the Vanderbilt Vaccine Research Program and associate professor of pediatrics at Vanderbilt; and Paul Spearman, M.D., director of the Division of Infectious Diseases at CCHMC. These clinical research sites are four of the ten Vaccine and Treatment Evaluation Units (VTEUs) comprising the IDCRC. The IDCRC’s Leadership Group also provides scientific oversight and operational support for this trial.

Investigators anticipate the trial will be fully enrolled by the end of April 2021. The results of this trial will inform further evaluation of vaccine variant strategies should an updated vaccine be required. The FDA recently issued guidance for vaccine developers seeking to amend an Emergency Use Authorization to address new variants. For more information about the study, visit ClinicalTrials.gov and search identifier NCT04785144.

The post New Phase 1 clinical trial of investigational vaccine against B.1.351 SARS-CoV-2 variant begins appeared first on Parenting Boss.