Clinical trial NCT06490367: Time-Restricted Eating in Huntington's Disease: A Clinical Pilot Study
Official title: Safety, Feasibility, and Biomarker Effects of Time-restricted Eating for 12 Weeks in Early-stage Huntington's Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Huntington Disease
Keywords: Time-restricted eating
Intermittent fasting
Time-restricted feeding
Dietary fasting
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2024-07-08
Enrollment: 22
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial examines whether 12 weeks of time-restricted eating (TRE), otherwise known as intermittent fasting, appears safe and feasible in persons with early-stage Huntington's disease (HD). The study also explores the effects of TRE on biomarkers and clinical measures associated with HD progression.

Detailed description: OBJECTIVES:

I. Examine the feasibility and tolerability of TRE through measures of protocol implementation, adherence rates, and adverse events.

II. Evaluate the safety of short-term TRE in the early stages of Huntington's disease (HD) by measures of body composition, vital signs, and blood analysis.

III. Analyze biomarker dynamics via peripheral markers of neurodegeneration and explore bioenergetic effects of TRE via measures of mitochondrial function.

IV. Explore whether TRE has effects on behavioral, cognitive, and motor function outcomes using standard HD clinical scales.

OUTLINE:

This study is a prospective interventional, open-label, single-arm trial. Enrolled participants are asked to engage in a TRE diet, specifically maintaining a 6-8-hour eating window every day for 12 weeks. Participants are allowed to self-select the timing of the eating window, but once selected, they are asked to maintain that schedule daily. Outside of that window, for the remaining 16-18 hours of day/night, participants are asked not to consume calorie-containing food or drink. Beverages without calories are allowed. The investigators measure body weight and composition, safety labs, adherence to the diet, dietary composition, sleep, physical activity, mood, biomarkers, and clinical outcomes. Data collection episodes take place at the Oregon Clinical and Translational Research Institute (OCTRI) within 7 days before the start of the study and again within 7 days after 12 weeks of TRE. Participants complete study surveys directly in Qualtrics.

Eligibility criteria: Inclusion Criteria:

Subjects eligible to participate in this study are persons who:

1. Are of at least 21 years of age at Screening.
2. Must fulfill one of the following criteria:

   1. Premanifest late prodromal HD as defined by a genetically confirmed CAG repeat greater than or equal to 36 and a CAG-Age Product (CAP) score greater than 368 (CAP = (Age) x (CAG - 33.66)).
   2. Early manifest (stage I and II) HD as defined by a TFC greater than or equal to 7. Subjects must have been determined to have a clinical diagnosis of HD by the site investigator as defined by a diagnostic confidence level (DCL) of 4.
3. Must fulfill both of the following criteria:

   1. Have undergone genetic testing with a known CAG repeat greater than or equal to 36.
   2. No features of juvenile HD (Westphal variant)

   Clarification of CAG Repeat Number (Allele length) Testing Requirements:

   A CAG repeat number obtained prior to the Screening Visit will be used to document subject eligibility if at Screening there is documentation available in the subject's record that states that the subject has an expanded CAG repeat (greater than or equal to 36) from a prior validated laboratory assessment.
4. All female subjects of childbearing potential must have a negative urine pregnancy test at baseline, and female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, a barrier method of birth control \[e.g. condoms with contraceptive foams, diaphragms with contraceptive jelly\], intrauterine devices, partner with vasectomy or sexual abstinence) for the duration of the study.
5. Are willing and capable of providing informed consent for study participation.
6. Are capable of reading, writing, and communicating effectively with others.

Exclusion Criteria:

Subjects ineligible to participate in this study are persons who:

1. Have participated in an investigational drug or device study within 30 days of the baseline visit
2. Have had previous neurosurgery for Huntington's disease or other movement disorders.
3. Have clinically significant cognitive impairment that hinders the ability to appropriately consent or adhere to detailed study directions, in the opinion of the principal investigator.
4. Have a presence of clinically significant psychosis and/or confusional states, in the opinion of the principal investigator.
5. Have clinically relevant hematologic, hepatic, cardiac, thyroid, or renal disease.
6. Have a history of substance abuse (based on DSMIV criteria) within the past 12 months prior to screening.
7. If female, are pregnant or breastfeeding.
8. Have a high-risk for nutritional deficiency.
9. Are not weight stable for at least three months prior to enrolling in the study, defined as greater than 2 kg change in body mass.
10. Express a desire to lose weight during the study.
11. Have a clinically significant medical, surgical, laboratory, or behavioral abnormality which in the judgment of the site Investigator makes the subject unsuitable for the study.
12. Have consistently practiced a time-restricted eating protocol within 3 months of trial onset.

Primary outcomes:
measure: Adherence to the TRE diet.
timeFrame: Week 1 to Week 13
Secondary outcomes:
measure: Change from baseline in fat-free body mass.
timeFrame: Baseline, Week 13
measure: Change from baseline in the daily eating period.
timeFrame: Baseline, Week 13
measure: Change from baseline in plasma neurofilament light protein (NfL).
timeFrame: Baseline, Week 13
measure: Change from baseline in plasma glial fibrillary acidic protein (GFAP).
timeFrame: Baseline, Week 13
measure: Change from baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS).
timeFrame: Baseline, Week 13
Other outcomes:
measure: Change from baseline in comprehensive metabolic panel values.
timeFrame: Baseline, Week 13
measure: Change from baseline in complete blood count values.
timeFrame: Baseline, Week 13
measure: Change from baseline in lipid panel values.
timeFrame: Baseline, Week 13
measure: Change from baseline in hemoglobin A1c.
timeFrame: Baseline, Week 13
measure: Change from baseline in creatinine clearance.
timeFrame: Baseline, Week 13
measure: Change from baseline in body weight.
timeFrame: Baseline - Week 13
measure: Evaluation of dietary composition
timeFrame: Baseline - Week 13
measure: Evaluation of sleep
timeFrame: Baseline - Week 13
measure: Evaluation of mood
timeFrame: Baseline - Week 13
measure: Evaluation of cognitive function
timeFrame: Baseline, Week 13
measure: Evaluation of physical activity
timeFrame: Baseline - Week 13
measure: Evaluation of mitochondrial function
timeFrame: Baseline, Week 13
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Amie Hiller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wells RG, Neilson LE, McHill AW, Hiller AL. Dietary fasting and time-restricted eating in Huntington's disease: therapeutic potential and underlying mechanisms. Transl Neurodegener. 2024 Apr 2;13(1):17. doi: 10.1186/s40035-024-00406-z.