Lifestyle Changes for Brain Health in Down Syndrome

(BOLD Trial)

Overseen By Jessica Danon

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Kansas Medical Center

Must not be taking: GLP-1, Anti-amyloid

Disqualifiers: Dementia, Insulin-dependent diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 months

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether losing weight or changing diet can help prevent or delay Alzheimer's disease in adults with Down syndrome. Participants will join either a weight loss group or a general health education group. The weight loss group will follow a low-calorie diet and use apps to track progress, while the other group will learn about general health topics. Individuals with Down syndrome who don't have dementia, have a BMI between 25 and 50, and can visit the University of Kansas Medical Center three times a year might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve health outcomes for individuals with Down syndrome.

Will I have to stop taking my current medications?

The trial requires that participants do not use GLP-1 medications or anti-amyloid medications. If you are taking these, you would need to stop before joining the study.

What prior data suggests that these lifestyle changes are safe for adults with Down syndrome?

Research has shown that weight loss programs for people with Down syndrome are generally safe. For instance, one study involving young people aged 13 to 26 found that a program combining healthy eating and exercise helped them lose weight over six months. Participants did not experience any serious side effects during this period. This suggests that losing weight through dietary changes is usually well-tolerated by people with Down syndrome. Since this trial focuses on a reduced-calorie diet with monthly education sessions, previous research suggests it will be safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how lifestyle changes, like diet and education, can improve brain health in individuals with Down syndrome. Unlike typical treatments which often focus on medication, this approach emphasizes a reduced calorie diet coupled with behavioral counseling and education. This method aims to empower individuals through sustainable, everyday changes that could potentially enhance their cognitive health. Additionally, the trial includes a comparison with general health education, which helps to highlight the specific benefits of targeted dietary and behavioral strategies. By focusing on lifestyle modifications, researchers hope to discover a non-invasive way to support brain health that complements existing medical treatments.

What evidence suggests that this trial's treatments could be effective for preventing Alzheimer's in adults with Down syndrome?

This trial will compare the effects of a weight loss intervention with a general health education control on brain health in individuals with Down syndrome. Research has shown that losing even a small amount of weight, like 2 kg, can improve thinking skills within six months. One study found that eating fewer calories and more fruits and vegetables linked to better brain health. Another study discovered that a specific diet, such as the ketogenic diet, improved thinking abilities in a person with both Down syndrome and dementia. Good nutrition plays a significant role in maintaining brain health throughout life. These findings suggest that dietary changes might help delay or prevent Alzheimer's in adults with Down syndrome. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with Down syndrome who are overweight, can speak, and live at home or in supported living. They need a caregiver to help with meals and transport to the University of Kansas Medical Center three times over a year. People with dementia, insulin-dependent diabetes, recent serious medical issues, dairy allergies, or MRI contraindications cannot join.

Inclusion Criteria

You have been diagnosed with Down syndrome.

Ability to communicate through spoken language

My BMI is between 25 and 45.

Exclusion Criteria

You are allergic to dairy.

You have been in a weight management program involving diet or exercise in the last 6 months.

You cannot have an MRI because you have metal implants, a pacemaker, or feel too anxious in small spaces.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either a weight loss group or a general health education control group. The weight loss group follows a reduced energy diet and attends monthly education sessions remotely, while the control group attends monthly health education sessions.

12 months

3 visits (in-person) at University of Kansas Medical Center

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive testing, MRI, and blood draws.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diet
• Health Education

Trial Overview The study tests if weight loss through diet changes prevents Alzheimer's in adults with Down syndrome. Participants will be randomly placed into two groups: one on a reduced energy diet using web apps for monitoring and another receiving general health education.

How Is the Trial Designed?

Group I: Weight Loss Experimental Treatment 2 Interventions

* Follow a reduced calorie diet daily for 12 months. * Attend monthly behavioral counseling/education

Group II: General Health Education Control Active Control 1 Intervention

\- Attend monthly health education sessions about general health.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

In a study of 61 non-demented adults with Down syndrome, higher levels of moderate-to-vigorous physical activity were positively associated with better cognitive functioning, while more sedentary behavior was linked to poorer cognitive performance.

Physical activity was found to influence white matter integrity in the brain, suggesting that staying active may help promote healthier cognitive aging in individuals with Down syndrome, although it did not show a direct association with Alzheimer's disease pathology markers like amyloid-β and tau.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity and cognitive and imaging biomarkers of Alzheimer's disease in down syndrome. Fleming, V., Piro-Gambetti, B., Patrick, A., et al.[2022]

This study aims to determine the total daily energy expenditure (TDEE) in a national sample of 230 youth with Down syndrome, using advanced methods like Doubly Labeled Water analysis to provide accurate measurements of body composition and energy needs.

By examining TDEE and related behaviors, the research seeks to develop predictive models for energy requirements and improve understanding of dietary and physical activity patterns, which are crucial for preventing and treating obesity in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy expenditure and weight-related behaviors in youth with Down syndrome: a protocol. Polfuss, M., Bandini, LG., Ravelli, MN., et al.[2023]

Children with Down syndrome (DS) showed significantly lower intake of fruits and leafy vegetables compared to children without DS, which may contribute to their higher risk of obesity and related health issues.

The study found that children with DS had higher fat mass and waist circumference measurements, indicating a concerning level of abdominal obesity that could lead to comorbidities like insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary pattern, physical activity and body composition of Children with and without Down Syndrome - A case control study. AlDarwish, N., AlSaab, A., AlQusair, D., et al.[2023]

Individuals with Down Syndrome (DS) are at a high risk of developing Alzheimer's disease (AD) by around 40 years of age due to increased levels of amyloid precursor protein (APP) on chromosome 21, which leads to higher production of the harmful Aβ peptide.

Targeting the dysregulation of β-secretase (BACE), which is involved in the production of Aβ, could be a promising therapeutic approach to prevent or delay Alzheimer's disease in individuals with Down Syndrome, thereby improving their quality of life as they age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Secretases, Alzheimer's Disease, and Down Syndrome. Webb, RL., Murphy, MP.[2022]

Treatment with corn oil, rich in linoleic and oleic acids, significantly improved hippocampus-dependent learning and memory in Ts65Dn mice, a model for Down syndrome, over a 30-day period.

The study demonstrated that corn oil treatment enhanced neurogenesis and dendritic maturation in the hippocampus of Ts65Dn mice, making their brain development comparable to that of normal mice, suggesting potential dietary interventions for cognitive benefits in individuals with Down syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with corn oil improves neurogenesis and cognitive performance in the Ts65Dn mouse model of Down syndrome. Giacomini, A., Stagni, F., Emili, M., et al.[2019]

In a study comparing 27 adults with Down syndrome (DS) and Alzheimer's disease (AD) to 30 adults with DS without AD, significant differences were found in living environments, with more individuals with AD residing in institutional settings, which may contradict recommendations for supportive care.

The findings suggest that lifestyle factors, especially living conditions, could play a role in the increased risk of Alzheimer's disease in adults with Down syndrome, highlighting the need for further research to inform preventive interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lifestyle factors and Alzheimer's disease in people with Down syndrome. Kenshole, AV., Gallichan, D., Pahl, S., et al.[2018]

Individuals with Down syndrome (DS) exhibit high levels of sedentary behavior, averaging 552 minutes per day, which is notably higher than reported levels in the general population, particularly among youth.

Interventions such as motor skills training have shown promise in reducing sedentary behavior in youth with DS, indicating that targeted strategies may be effective in addressing this health disparity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of sedentary behaviour in people with Down syndrome across the lifespan: A clarion call. Agiovlasitis, S., Choi, P., Allred, AT., et al.[2020]

In a study of 131 individuals with intellectual disabilities, nearly half (46.8%) were classified as obese, highlighting a significant prevalence of obesity in this population compared to the general population.

Participants had poor dietary quality, with average energy intakes from sugar, fat, and saturated fat exceeding recommended levels, and many did not meet the daily requirements for essential micronutrients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An examination of the nutritional intake and anthropometric status of individuals with intellectual disabilities: Results from the SOPHIE study. Hoey, E., Staines, A., Walsh, D., et al.[2018]

In a study of 23 adults with Down syndrome, it was found that women had higher fat mass and lower lean mass and bone mass compared to men, with these body composition metrics worsening with age.

The majority of participants had inadequate intakes of essential nutrients like vitamin D and iodine, and 82% consumed fewer than 5 servings of fruits and vegetables daily, indicating a need for improved dietary habits to enhance their health and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imbalanced dietary patterns, anthropometric, and body composition profiles amongst adults with Down syndrome. Herrera-Quintana, L., Vázquez-Lorente, H., Carranco Romo, MJ., et al.[2022]

Maternal choline supplementation (MCS) significantly increased the number and density of cholinergic neurons in the brains of Ts65Dn mice, a model for Down syndrome, suggesting it can protect against degeneration associated with the condition.

MCS also rescued a previously unexplored population of GABAergic neurons, indicating its potential as a neuroprotective treatment not only for Down syndrome but also for broader aging-related neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease. Gautier, MK., Kelley, CM., Lee, SH., et al.[2023]

A study involving 599 children with Down syndrome found that the most common co-occurring medical conditions included vision (72.5%), ear/hearing (71.0%), and gastrointestinal issues (61.3%), highlighting the need for comprehensive medical care.

Children with Down syndrome who also had neurodevelopmental (ND) and mental health (MH) conditions, such as autism spectrum disorder and ADHD, experienced a higher frequency of medical issues, indicating a complex relationship between these conditions that must be considered in clinical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-occurring conditions in Down syndrome: Findings from a clinical database. Baumer, NT., Hojlo, MA., Pawlowski, KG., et al.[2023]

In a study of 21 adolescents and young adults with Down syndrome, those who received parent training in behavioral intervention alongside nutrition and activity education lost an average of 3.2 kg more than those who only received nutrition and activity education after 6 months, with results sustained at 1 year.

The behavioral intervention group also increased their moderate/vigorous physical activity by 18 minutes per day compared to baseline, while the other group decreased their activity, highlighting the effectiveness of the combined approach in promoting healthier lifestyles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parent support improves weight loss in adolescents and young adults with Down syndrome. Curtin, C., Bandini, LG., Must, A., et al.[2021]

Children with Down syndrome (DS) showed high adherence to the Mediterranean diet and physical activity levels, which were linked to a lower risk of being overweight or obese, based on a study of 61 children.

The study found that higher physical activity levels were associated with healthier HDL cholesterol levels, suggesting that children with DS can achieve similar health outcomes as their peers without DS when following a good diet and being active.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mediterranean diet and physical activity in Down syndrome pediatric subjects: the DONUT STUDY. Pecoraro, L., Solfa, M., Ferron, E., et al.[2022]

Down syndrome (DS) is caused by an extra copy of chromosome 21 and is associated with various health issues, including intellectual disability, early onset Alzheimer's, and nutritional disorders like obesity and vitamin deficiencies.

Early dietary interventions can significantly improve the quality of life for individuals with DS by reducing the risk of associated health conditions and enhancing their overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Down syndrome--genetic and nutritional aspects of accompanying disorders. Mazurek, D., Wyka, J.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12056299/

Brain outcomes with lifestyle change in adults with Down ... Intentional modest weight loss of even 2 kg among trial participants was associated with improvements in cognition at a 6‐month follow‐up.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05985486

Brain Outcomes With Lifestyle Change in Down Syndrome A reduced calorie diet which uses frozen meals purchased at the store and focuses on increasing fruits and vegetables associated with brain health.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9870323/

Case report: Ketogenic diet acutely improves cognitive ... A therapeutic ketogenic diet was associated with significant cognitive improvement in this patient with concurrent Down syndrome and dementia. Keywords: ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772408524001376

The dynamic influence of nutrition on prolonged cognitive ... This review explores the impact of nutrition, specifically energy and bioactive components, on cognitive health across different life stages.

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Brain outcomes with lifestyle change in adults with Down ... A randomized trial that will evaluate the impact of weight loss and dietary intake on factors that may delay the development of AD in adults with DS.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022347613008512

Parent Support Improves Weight Loss in Adolescents and ... Twenty-one patients with Down syndrome aged 13-26 years with a body mass index ≥85th percentile were enrolled and randomized to a 6-month nutrition and activity ...

7. researchgate.net researchgate.net/publication/356607884_Weight_Management_of_Young_Women_with_Down_Syndrome_C-ICAN_Meal_Plan

Weight Management of Young Women with Down Syndrome intervention. Results Weight was obtained from 92(84%) and 89(81%) randomized adolescents at 12 and 18 months, respectively. Weight change ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11937868/

Weight‐loss interventions for adolescents with Down syndrome Obesity in adolescents with DS has been associated with several negative health outcomes, including obstructive sleep apnea, insulin resistance, ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9937587/

Weight management recommendations for youth with Down ... Youth with Down syndrome (DS) have a higher prevalence of overweight and obesity compared to the general youth population.

10. mdpi.com mdpi.com/2227-9067/10/1/36

Nutrition as Prevention of Diet-Related Diseases—A Cross ... The aim of this study was to assess the diet of children with Down syndrome (DS) and to identify potential dietary mistakes made by their parents.