Neuroprotection by Cannabinoids in Huntington's Disease

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

Sponsors

Lead Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Collaborator: GW Pharmaceuticals Ltd.

Source Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Brief Summary

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

Overall Status Completed
Start Date 2011-09-01
Completion Date 2012-06-01
Primary Completion Date 2012-06-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Serious Adverse Events reported 8 months
Changes in the UHDRs Score On week 4 and 12 of each period
Secondary Outcome
Measure Time Frame
Changes in the BDNF levels (Brain-derived Neurotrophic Factor), oxidative stress (due to mitochondrial dysfunction) and proinflammatory cytokines in plasma 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. On week 12 of each period
Enrollment 25
Condition
Intervention

Intervention Type: Drug

Intervention Name: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)

Description: 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.

Arm Group Label: Sativex

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo, One spray per day, up to a maximum of 12 sprays per day.

Arm Group Label: Placebo

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Justo García de Yébenes Principal Investigator Hospital Universitario Ramón y Cajal
Location
Facility: Hospital Universitario Ramón y Cajal
Location Countries

Spain

Verification Date

2013-01-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Sativex

Type: Experimental

Label: Placebo

Type: Placebo Comparator

Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

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