Neuroprotection by Cannabinoids in Huntington's Disease

Huntington's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01502046
• Other study ID #: SAT-HD
• Secondary ID: 2010-024227-24
• Status: Completed
• Phase: Phase 2
• First received: December 29, 2011
• Last updated: January 31, 2013
• Start date: September 2011
• Est. completion date: June 2012

Study information

• Verified date: January 2013
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Universitario Ramón y Cajal	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal	GW Pharmaceuticals Ltd.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serious Adverse Events reported		8 months	No
Primary	Changes in the UHDRs Score	UHDRS scale scores from the following perspectives: motor, cognitive, psychiatric and functional.	On week 4 and 12 of each period	No
Secondary	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	No
Secondary	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	No