Resveratrol and Huntington Disease (REVHD)

• ClinicalTrials.gov Identifier: NCT02336633
• Recruitment Status: Completed
• First Posted: January 13, 2015
• Last Update Posted: February 5, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: January 8, 2015
• First Posted Date: January 13, 2015
• Last Update Posted Date: February 5, 2020
• Study Start Date: July 2015
• Actual Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 8, 2015)

rate of caudate atrophy [ Time Frame: 1 year ]

Measurement of the rate of caudate atrophy before and after one year of treatment with resveratrol in early affected HD patients using volumetric MRI.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 8, 2015)

• UHDRS (Unified Huntington Disease Rating Scale) [ Time Frame: 1 year ]
• TFC (Total Functional Capacity) [ Time Frame: 1 year ]
• ratio of inorganic phosphate/phosphocreatine [ Time Frame: 1 year ]
  The benefit of resveratrol on brain energy metabolism will be evaluated by the restoration of an increased ratio of inorganic phosphate/phosphocreatine - reflecting normal brain activation - during visual stimulation, using 31P-MRS will be assessed before and after 1 year of treatment

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Resveratrol and Huntington Disease
• Official Title: Metabolic Intervention Using Resveratrol in Patients With Huntington Disease
• Brief Summary: The purpose of this study is to evaluate the therapeutic potential of Resveratrol on the caudate volume in HD patients, using volumetric MRI.

Detailed Description

Thanks to neuroimaging biomarkers already validated in HD and the newly identified metabolic brain biomarkers using 31P-MRS, we can test for a reduction in neurodegeneration among HD patients resulting from an improvement in brain energy profiles with resveratrol.

We plan to randomize 102 early affected HD patients (with a maximum of 120 included patients) in France (5≤UHDRS≤40) in a randomized, double-blind, controlled study. Patients will receive either resveratrol at 80 mg (n=51), or placebo (n=51) for 12 months. Clinical benefit will be respectively evaluated by UHDRS and neuropsychiatric questionnaires; biological tolerance will be evaluated by routine biochemical blood tests and plasma measurements of resveratrol, these three factors will be tested every three months.

The primary end-point will be the measure of the rate of caudate atrophy - the most sensitive biomarker identified to date in HD - after one year of treatment with resveratrol in early affected HD patients using volumetric MRI as we described.

Secondary end-points include:

The clinical and biological tolerance of resveratrol in HD patients will be evaluated by (i) neuropsychiatric questionnaires: Starkstein apathy scale, Hospital Anxiety and Depression Scale (HADS), Systems Behaviour Inventory (FrSBe) and SF36, (ii) a cognitive test; Symbol Digit Modalities Test (SDMT) and (iii) routine biochemical tests The clinical benefit of resveratrol will be evaluated by a decrease in the progression of the UHDRS over a year of treatment The benefit of resveratrol on brain energy metabolism will be evaluated by the restoration of an increased ratio of inorganic phosphate/phosphocreatine - reflecting normal brain activation - during visual stimulation, using 31P-MRS as we described The progression of caudate atrophy over a year will be correlated with the changes in brain energy profile as well as changes in the progression of the UHDRS.

The compliance of treatment and peak in plasmatic concentration through plasma measurements of resveratrol.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Huntington Disease

Intervention

• Dietary Supplement: Resveratrol
  2 capsules of 20mg in the morning and in the evening (4 capsules in total/day = 80mg/day) every day during 1 year
• Other: Placebo

Study Arms

• Experimental: 1
  Resveratrol (80mg/j = 4 capsules/day)
  Intervention: Dietary Supplement: Resveratrol
• Placebo Comparator: 2
  Placebo (4 capsules/day)
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 8, 2015): 102
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2020
• Actual Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria :

• Positive genetic test with CAG repeat length > or = 39 in HTT gene
• At least 18 years of age
• Signature of the informed consent
• Covered by social security
• UHDRS score between 5 and 40 (both included)
• Ability to undergo MRI scanning

Exclusion criteria :

• Hypersensitivity to resveratrol or to one of its excipients (gelatin and glycerin)
• Tetrabenazine treatment
• Neuroleptic treatments other than olanzapine at small doses (≤10 mg) and Abilify® (≤15mg)
• VKA treatment (Previscan®, Sintron®, Coumadine®)
• NACO treatment (Pradaxa®, Xarelto®, Eliquis®)
• Additional psychiatric or neurological conditions
• Severe head injury
• Participation in another therapeutic trial (3 months exclusion period)
• Pregnancy and breastfeeding
• Inability to understand information about the protocol
• Persons deprived of their liberty by judicial or administrative decision
• Adult subject under legal protection or unable to consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02336633
• Other Study ID Numbers: P130918
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Assistance Publique - Hôpitaux de Paris
• Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fanny Mochel, MD, PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: August 2019