Neuroprotection by Cannabinoids in Huntington's Disease
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| ClinicalTrials.gov Identifier: NCT01502046 |
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Recruitment Status :
Completed
First Posted : December 30, 2011
Last Update Posted : February 1, 2013
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Huntington's Disease | Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 25 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Double (Participant, 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 |
| Study Start Date : | September 2011 |
| Actual Primary Completion Date : | June 2012 |
| Actual Study Completion Date : | June 2012 |
| Arm | Intervention/treatment |
|---|---|
| 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. |
- Serious Adverse Events reported [ Time Frame: 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.
- 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 ]
- 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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01502046
| Spain | |
| Hospital Universitario Ramón y Cajal | |
| Madrid, Spain, 28034 | |
| Principal Investigator: | Justo García de Yébenes | Hospital Universitario Ramón y Cajal |
| Responsible Party: | Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal |
| ClinicalTrials.gov Identifier: | NCT01502046 |
| Other Study ID Numbers: |
SAT-HD 2010-024227-24 ( EudraCT Number ) |
| First Posted: | December 30, 2011 Key Record Dates |
| Last Update Posted: | February 1, 2013 |
| Last Verified: | January 2013 |
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Huntington's disease, cannabinoids |
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Huntington Disease 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 Cognition Disorders Neurocognitive Disorders Mental Disorders |
Dronabinol Cannabidiol Anticonvulsants Hallucinogens Physiological Effects of Drugs Psychotropic Drugs Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Cannabinoid Receptor Agonists Cannabinoid Receptor Modulators Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Hormones |