Lifestyle Changes for Brain Health in Down Syndrome

(BOLD Trial)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Kansas Medical Center

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

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

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this study is to determine if weight loss or changes in dietary intake can help prevent of delay adults with Down syndrome from developing Alzheimer's Disease Adults with Down syndrome without dementia will be randomized to either a weight loss group or a general health education control group. The weight loss group will be asked to follow a reduced energy diet, attend monthly education sessions delivered remotely and self-monitor diet and body weight using commercially available web-based applications. The control group will be asked to attend remotely delivered monthly education sessions on general health education topics. All participants will come to the University of Kansas Medical Center, 3 times across 12 months for a blood draw, cognitive testing, a MRI, assessment of height and weight, and assessment of diet intake.

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 data supports the effectiveness of the treatment 'Lifestyle Changes for Brain Health in Down Syndrome'?

Research suggests that early dietary interventions and parent support in nutrition and activity education can improve health outcomes in individuals with Down syndrome, potentially delaying associated conditions and improving quality of life. ^{1 2 3 4 5}

Is the lifestyle intervention for brain health in Down syndrome safe?

The research articles do not provide specific safety data for the lifestyle intervention, but they highlight the importance of addressing obesity and poor diet quality in individuals with Down syndrome, which suggests that lifestyle changes focusing on healthy diet and physical activity are generally considered safe and beneficial. ^{3 6 7 8 9}

How does the diet treatment for brain health in Down syndrome differ from other treatments?

The diet treatment for brain health in Down syndrome is unique because it focuses on using natural dietary components, like fatty acids found in corn oil, to enhance brain function and neurogenesis (the growth of new brain cells) without adverse effects. This approach contrasts with other treatments that may involve medications with potential side effects. ^{10 11 12 13 14}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Diet (Behavioral Intervention)
• Health Education (Behavioral Intervention)

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.

Participant Groups

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+

Dr. Steve Stites

University of Kansas Medical Center

Chief Executive Officer

MD from University of Kansas School of Medicine

Dr. Matthias Salathe

University of Kansas Medical Center

Chief Medical Officer

MD from University of Kansas School of Medicine

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Down syndrome--genetic and nutritional aspects of accompanying disorders. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Dietary pattern, physical activity and body composition of Children with and without Down Syndrome - A case control study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Imbalanced dietary patterns, anthropometric, and body composition profiles amongst adults with Down syndrome. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Parent support improves weight loss in adolescents and young adults with Down syndrome. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Mediterranean diet and physical activity in Down syndrome pediatric subjects: the DONUT STUDY. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Systematic review of sedentary behaviour in people with Down syndrome across the lifespan: A clarion call. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Co-occurring conditions in Down syndrome: Findings from a clinical database. [2023]

8. England pubmed.ncbi.nlm.nih.gov

An examination of the nutritional intake and anthropometric status of individuals with intellectual disabilities: Results from the SOPHIE study. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Energy expenditure and weight-related behaviors in youth with Down syndrome: a protocol. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Treatment with corn oil improves neurogenesis and cognitive performance in the Ts65Dn mouse model of Down syndrome. [2019]

11. United States 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

β-Secretases, Alzheimer's Disease, and Down Syndrome. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Lifestyle factors and Alzheimer's disease in people with Down syndrome. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Physical activity and cognitive and imaging biomarkers of Alzheimer's disease in down syndrome. [2022]