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Neuroprotection by Cannabinoids in Huntington's Disease

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ClinicalTrials.gov Identifier: NCT01502046
Recruitment Status : Completed
First Posted : December 30, 2011
Last Update Posted : February 1, 2013
Sponsor:
Collaborator:
GW Pharmaceuticals Ltd.
Information provided by (Responsible Party):
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Tracking Information
First Submitted Date  ICMJE December 29, 2011
First Posted Date  ICMJE December 30, 2011
Last Update Posted Date February 1, 2013
Study Start Date  ICMJE September 2011
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 29, 2011)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01502046 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 30, 2011)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 29, 2011)
  • Changes in the BDNF levels (Brain-derived Neurotrophic Factor), oxidative stress (due to mithocondrial dysfunction) and proinflamatory citokines 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 mithocondrial dysfunction) and proinflamatory citokines in cerebrospinal fluid. [ Time Frame: On week 12 of each period ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neuroprotection by Cannabinoids in Huntington's Disease
Official Title  ICMJE A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington's Disease
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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Huntington's Disease
Intervention  ICMJE
  • 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.
  • Drug: Placebo
    Placebo, One spray per day, up to a maximum of 12 sprays per day.
Study Arms  ICMJE
  • Experimental: Sativex
    Intervention: Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * López-Sendón Moreno JL, García Caldentey J, Trigo Cubillo P, Ruiz Romero C, García Ribas G, Alonso Arias MA, García de Yébenes MJ, Tolón RM, Galve-Roperh I, Sagredo O, Valdeolivas S, Resel E, Ortega-Gutierrez S, García-Bermejo ML, Fernández Ruiz J, Guzmán M, García de Yébenes 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 29, 2011)
25
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01502046
Other Study ID Numbers  ICMJE SAT-HD
2010-024227-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Study Sponsor  ICMJE Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Collaborators  ICMJE GW Pharmaceuticals Ltd.
Investigators  ICMJE
Principal Investigator: Justo García de Yébenes Hospital Universitario Ramón y Cajal
PRS Account Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP