Neuroprotection by Cannabinoids in Huntington's Disease

NCT01502046 | Completed Phase 2

• 2 other identifiers: SAT-HD2010-024227-24
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Conditions

Huntington's Disease

Keywords

Huntington's disease, cannabinoids

Outcome Measures

Primary Outcomes (2)

• Serious Adverse Events reported

  8 months

• 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

Secondary Outcomes (2)

• 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

Study Arms (2)

Sativex

EXPERIMENTAL

Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) DRUG

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.

Sativex

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with HD
• Older than 18 years.
• Able to understand the study, to attend the study visits and to provide informed consent.
• Stable baseline medication for at least 6 weeks prior to randomization.
• Score in the UHDRS-motor from 5 to 50.
• 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.
• Not consumers of products derived from marijuana.

You may not qualify if:

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

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead
• GW Pharmaceuticals Ltd: collaborator

Study Sites (1)

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

Related Publications (1)

• Lopez-Sendon Moreno JL, Garcia Caldentey J, Trigo Cubillo P, Ruiz Romero C, Garcia Ribas G, Alonso Arias MA, Garcia de Yebenes MJ, Tolon RM, Galve-Roperh I, Sagredo O, Valdeolivas S, Resel E, Ortega-Gutierrez S, Garcia-Bermejo ML, Fernandez Ruiz J, Guzman M, Garcia de Yebenes Prous J. A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington's disease. J Neurol. 2016 Jul;263(7):1390-400. doi: 10.1007/s00415-016-8145-9. Epub 2016 May 9.

  PMID: 27159993 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

Dronabinol; Cannabidiol

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Justo García de Yébenes

  Hospital Universitario Ramón y Cajal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2011
• First Posted: December 30, 2011
• Study Start: September 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: February 1, 2013

Record last verified: 2013-01

Locations

ES (1)