Neuroprotection by Cannabinoids in Huntington's Disease

January 31, 2013 updated by: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington's Disease

Huntington's disease (HD) is a progressive neurodegenerative disorder, related to an abnormal expansion of CAG triplets in the huntingtin gene, characterized by motor, cognitive and behavioral abnormalities, without known effective symptomatic treatment and without known disease slowing strategy. The most severe neuropathological lesions observed in HD take place in the striatum, one brain area important in motor control and rich in cannabinoid receptors (CBR). CBR are subdivided in two classes: CB1R are located in neurons and play a role in neuronal function; CB2R in brain are located mostly in microglia and modulate neuroinflammation.

CBR disappear early in the course of HD, before there is a massive drop out of cells in the striatum. Cannabinoid transmission is also an early event in brains of animal models of HD. In R6/2 mice, which carry large CAG expansions and develop an early and severe HD phenotype the suppression of the CB1R gene further accelerate the development of a severe clinical syndrome and the characteristic brain inclusions and abnormalities of synaptic density. R6/2 treated mice treated with cannabinoids improve their clinical phenotype, their brain lesions, the synaptic density and the levels of BNDF, a neurotrophic factor which enhances survival and resistance of striatal neurons.

Preliminary studies of cannabinoids in patients with HD have shown that these compounds are safe in these patients. Those studies, however, did not show efficacy because 1) they were underpowered from the statistical point of view, 2) were performed with isolated pure cannabinoids, instead of the more physiological stimulation with a mixture of compounds, and 3) they did use insensitive clinical parameters instead of sensitive end points, such as pathogenically important biomarkers.

The investigators propose a phase II trial with combination of cannabinoids with evaluation of safety, by the profile of adverse events, and efficacy, according to changes of important biomarkers

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon Y Cajal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with HD
  2. Older than 18 years.
  3. Able to understand the study, to attend the study visits and to provide informed consent.
  4. Stable baseline medication for at least 6 weeks prior to randomization.
  5. Score in the UHDRS-motor from 5 to 50.
  6. Good cognitive status (MMSE> 25) at the screening visit, with no evidence of major depression, at the discretion of the attending physician, and no evidence of psychosis.
  7. Not consumers of products derived from marijuana.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. History of drug addition.
  3. History of psychosis or with history of suicidal attempt.
  4. Patients with diseases of the oral cavity that prevents the safe administration of the drug.
  5. Patients in which drug administration is contraindicated according to the SmPC

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo, One spray per day, up to a maximum of 12 sprays per day.
Experimental: Sativex
Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
Sativex 2.7 mg delta-9-tetrahydrocannabinol/2.5 mg cannabidiol Oromucosal Spray. One spray per day, up to a maximum of 12 sprays per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serious Adverse Events reported
Time Frame: 8 months
8 months
Changes in the UHDRs Score
Time Frame: On week 4 and 12 of each period
UHDRS scale scores from the following perspectives: motor, cognitive, psychiatric and functional.
On week 4 and 12 of each period

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in the BDNF levels (Brain-derived Neurotrophic Factor), oxidative stress (due to mitochondrial dysfunction) and proinflammatory cytokines in plasma
Time Frame: Basal and on week 4 and 12 of each period
Basal and on week 4 and 12 of each period
Changes in the BDNF levels (Brain-derived Neurotrophic Factor), oxidative stress (due to mitochondrial dysfunction) and proinflammatory cytokines in cerebrospinal fluid.
Time Frame: On week 12 of each period
On week 12 of each period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Collaborators

Jazz Pharmaceuticals

Investigators

  • Principal Investigator: Justo García de Yébenes, Hospital Universitario Ramon Y Cajal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

December 29, 2011

First Submitted That Met QC Criteria

December 29, 2011

First Posted (Estimate)

December 30, 2011

Study Record Updates

Last Update Posted (Estimate)

February 1, 2013

Last Update Submitted That Met QC Criteria

January 31, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAT-HD
  • 2010-024227-24 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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