Neuroprotection by Cannabinoids in Huntington's Disease

This study has been completed.
Sponsor:
Collaborator:
GW Pharmaceuticals Ltd.
Information provided by (Responsible Party):
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier:
NCT01502046
First received: December 29, 2011
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Huntington's Disease
Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington's Disease

Resource links provided by NLM:


Further study details as provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:

Primary Outcome Measures:
  • Serious Adverse Events reported [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Changes in the UHDRs Score [ Time Frame: On week 4 and 12 of each period ] [ Designated as safety issue: No ]
    UHDRS scale scores from the following perspectives: motor, cognitive, psychiatric and functional.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: September 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Placebo Comparator: Placebo Drug: Placebo
Placebo, One spray per day, up to a maximum of 12 sprays per day.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01502046

Locations
Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Sponsors and Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
GW Pharmaceuticals Ltd.
Investigators
Principal Investigator: Justo García de Yébenes Hospital Universitario Ramón y Cajal
  More Information

No publications provided

Responsible Party: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier: NCT01502046     History of Changes
Other Study ID Numbers: SAT-HD, 2010-024227-24
Study First Received: December 29, 2011
Last Updated: January 31, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:
Huntington's disease, cannabinoids

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dementia
Chorea
Dyskinesias
Tetrahydrocannabinol
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014