Resveratrol and Huntington Disease - Full Text View

Purpose

The purpose of this study is to evaluate the therapeutic potential of Resveratrol on the caudate volume in HD patients, using volumetric MRI.

Condition	Intervention	Phase
Huntington Disease	Dietary Supplement: Resveratrol Other: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Metabolic Intervention Using Resveratrol in Patients With Huntington Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Huntington disease chorea-acanthocytosis

MedlinePlus related topics: Huntington's Disease

Drug Information available for: Resveratrol

Genetic and Rare Diseases Information Center resources: Huntington Disease

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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


Estimated Enrollment:	102
Study Start Date:	July 2015
Estimated Study Completion Date:	January 2019
Estimated Primary Completion Date:	January 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Resveratrol (80mg/j = 4 capsules/day)	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
Placebo Comparator: 2 Placebo (4 capsules/day)	Other: Placebo

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria :

Positive genetic test with CAG repeat length > 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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02336633

Contacts


Contact: Tiffany Monier, M.Sc.	+33 1 57 27 42 22	tiffany.monnier@icm-institute.org

Locations


France
Institut du Cerveau et de la Moelle, Hôpital de la Pitié Salpêtrière	Recruiting
Paris, France, 75013
Contact: Tiffany Monnier, M Scs

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators


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

More Information


Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT02336633 History of Changes
Other Study ID Numbers:	P130918
Study First Received:	January 8, 2015
Last Updated:	September 14, 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Huntington disease Neurodegenerative disease Volumetric MRI	31P MR spectroscopy metabolism Caudate atrophy

Additional relevant MeSH terms:


Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Dementia Chorea Dyskinesias Movement Disorders Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Cognition Disorders Neurocognitive Disorders Mental Disorders	Resveratrol Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Antineoplastic Agents, Phytogenic Antineoplastic Agents Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 17, 2017

Resveratrol and Huntington Disease (REVHD)