Time-Restricted Eating for Huntington's Disease

(TREHD Trial)

Overseen By Russell Wells, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

Disqualifiers: Cognitive impairment, Psychosis, Substance abuse, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether time-restricted eating, a form of intermittent fasting, is safe and practical for individuals with early-stage Huntington's disease (HD). Researchers aim to determine if this eating pattern affects biomarkers, which indicate disease progression. The trial is open to those with early signs of HD who have undergone genetic testing confirming the disease. Participants should not have experienced recent weight changes or practiced fasting recently. As an unphased trial, this study offers a unique opportunity to contribute to understanding new lifestyle interventions for HD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that time-restricted eating is safe for individuals with Huntington's disease?

Research has shown that time-restricted eating (TRE), a form of intermittent fasting where eating occurs only during certain hours each day, is generally safe. One study examined TRE in healthy middle-aged and older adults and found it was well-tolerated, with most participants experiencing no significant negative effects. Another study focused on individuals with early-stage Huntington's disease (HD) and found similar results. Many participants followed TRE for over a year without major issues. These findings suggest TRE could be a safe option for managing HD. However, it is important to consult a healthcare provider before starting any new diet plan. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Time-Restricted Eating is unique because it offers a non-pharmacological approach to managing Huntington's Disease, which is usually treated with medications like tetrabenazine and antipsychotics to manage symptoms. Unlike these medications, which can have significant side effects, Time-Restricted Eating focuses on dietary habits, potentially offering a safer and more natural way to influence disease progression. Researchers are excited about this method because it may improve cellular health and brain function by aligning eating patterns with the body's natural circadian rhythms, providing a novel way to address the underlying mechanisms of the disease.

What evidence suggests that time-restricted eating might be an effective treatment for Huntington's disease?

Research has shown that time-restricted eating (TRE), also known as intermittent fasting, might help treat Huntington's disease. Studies suggest that TRE could aid in removing the harmful huntingtin protein, a major issue in Huntington's. It might also restore levels of a protein that supports brain health and improve cellular energy production. In other brain diseases, TRE has reduced brain inflammation and promoted brain cell growth. These findings make TRE a promising approach for managing Huntington's disease symptoms. ^{1 2 4 6 7}

Who Is on the Research Team?

Amie Hiller, MD

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This clinical trial is for individuals with early-stage Huntington's Disease who are interested in trying a time-restricted eating diet, also known as intermittent fasting, for 12 weeks. Specific eligibility criteria details were not provided.

Inclusion Criteria

I have a genetic test showing CAG repeat ≥ 36 without signs of juvenile Huntington's.

I am not pregnant and will use effective birth control.

I am at least 21 years old.

Exclusion Criteria

I have had brain surgery for Huntington's disease or another movement disorder.

I have significant blood, liver, heart, thyroid, or kidney disease.

I want to lose weight during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants engage in a time-restricted eating (TRE) diet for 12 weeks, maintaining a 6-8 hour eating window each day.

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the TRE intervention, including biomarker analysis and clinical assessments.

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Time-Restricted Eating Diet

Trial Overview The study is testing the safety and feasibility of a time-restricted eating diet over a period of 12 weeks in people with early-stage Huntington's Disease. It will also assess how this diet affects certain biomarkers and clinical measures related to the disease's progression.

How Is the Trial Designed?

Group I: Time-Restricted Eating Experimental Treatment 1 Intervention

All participants are assigned to this arm.

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

A ketogenic diet (KD) in a mouse model of Huntington's disease (BACHD mice) improved sleep/wake cycles by increasing daytime sleep and enhancing sleep onset timing, which is significant given the common sleep disturbances in HD patients.

The KD also improved motor performance in tests and showed potential to delay disease progression, highlighting the importance of dietary interventions as a therapeutic strategy for managing Huntington's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington's disease. Whittaker, DS., Tamai, TK., Bains, RS., et al.[2023]

Individuals with Huntington's disease often experience dysphagia, leading to the need for texture-modified diets, which can reduce sensory stimulation and enjoyment of food.

The commentary highlights two clinical interventions designed to enhance dietary satisfaction and encourage involvement in food preparation for people with Huntington's disease, suggesting a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term use of Modified Diets in Huntington's Disease: A Descriptive Clinical Practice Analysis on Improving Dietary Enjoyment. Moorhouse, B., Fisher, CA.[2016]

In a study of 1001 premanifest Huntington disease carriers, adherence to the Mediterranean diet did not significantly affect the time to phenoconversion, indicating that this diet may not be a protective factor against the onset of Huntington disease.

However, higher dairy consumption was linked to a two-fold increased risk of phenoconversion, suggesting that certain dietary components may influence disease progression and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease. Marder, K., Gu, Y., Eberly, S., et al.[2021]

Huntington's disease (HD) patients have significantly higher energy intake compared to age- and gender-matched controls, with symptomatic patients consuming even more calories, indicating a potential link between dietary habits and disease severity.

The study found differences in adherence to the Mediterranean Diet (MD) between HD patients and controls, suggesting that dietary patterns may influence disease outcomes and highlighting the need for nutritional education in managing HD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the Dietary Intake Using the CyFFQ Semi-Quantitative Food Frequency Questionnaire in Cypriot Huntington's Disease Patients. Christodoulou, CC., Demetriou, CA., Philippou, E., et al.[2023]

In a study of 43 presymptomatic individuals with a genetic risk for Huntington disease, those who later developed motor symptoms had significantly lower brain glucose metabolism in the caudate region compared to those who remained symptom-free, indicating a potential biomarker for disease onset.

The study found that measuring brain glucose uptake improved predictions of the age at onset of Huntington disease by 37%, suggesting that glucose metabolism may play a critical role in the progression of the disease beyond just genetic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size. Ciarmiello, A., Giovacchini, G., Orobello, S., et al.[2021]

A 41-year-old man with progressive Huntington's disease showed significant improvements in motor symptoms (52% improvement) and daily living activities (28% improvement) after following a time-restricted ketogenic diet for 48 weeks.

The ketogenic diet also led to notable enhancements in behavior problems related to HD (50-100% improvement) and quality of life (25% improvement), with no significant adverse effects reported, indicating a potential safe dietary intervention for managing symptoms of HD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-Restricted Ketogenic Diet in Huntington's Disease: A Case Study. Phillips, MCL., McManus, EJ., Brinkhuis, M., et al.[2022]

Dietary restriction (DR) in the YAC128 mouse model of Huntington's disease significantly improved metabolic and motor functions, correcting issues like increased body weight and impaired motor skills.

DR was associated with reduced levels of the harmful human HTT protein and changes in gene expression related to histone acetylation, suggesting a potential mechanism for its protective effects against Huntington's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protection by dietary restriction in the YAC128 mouse model of Huntington's disease: Relation to genes regulating histone acetylation and HTT. Moreno, CL., Ehrlich, ME., Mobbs, CV.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10986006/

Dietary fasting and time-restricted eating in Huntington's disease We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial ...

2. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0319253

Time-restricted eating in early-stage Huntington's disease The primary outcome measure will be the percent of days participants adhere to the TRE diet. ... Time-restricted ketogenic diet in Huntington's disease: a case ...

3. ctv.veeva.com ctv.veeva.com/study/time-restricted-eating-in-huntingtons-disease-a-clinical-pilot-study

Time-Restricted Eating in Huntington's Disease: A Clinical ... This trial examines whether 12 weeks of time-restricted eating (TRE), otherwise known as intermittent fasting, appears safe and feasible in ...

4. researchgate.net researchgate.net/publication/379506154_Dietary_fasting_and_time-restricted_eating_in_Huntington's_disease_therapeutic_potential_and_underlying_mechanisms

(PDF) Dietary fasting and time-restricted eating in ... We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial function and stress- ...

5. mdpi.com mdpi.com/2072-6643/17/14/2266

Intermittent Fasting as a Neuroprotective Strategy: Gut– ... In neurodegenerative models, time-restricted feeding has been shown to reduce hippocampal inflammation, enhance neurogenesis, and restore circadian expression ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06490367

Time-Restricted Eating in Huntington's Disease: A ... This trial examines whether 12 weeks of time-restricted eating (TRE), otherwise known as intermittent fasting, appears safe and feasible in persons with early- ...

7. researchgate.net researchgate.net/publication/390173342_Time-restricted_eating_in_early-stage_Huntington's_disease_A_12-week_interventional_clinical_trial_protocol

Time-restricted eating in early-stage Huntington's disease Results Among 116 respondents, 42% reported practicing a fasting protocol, with 36% sustaining it for over a year and 40% applying it as a ...