Huntington's DiseasePhase 2NCT01502046
Neuroprotection by Cannabinoids in Huntington's Disease
A Phase 2 study testing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in people with Huntington's Disease, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Huntington's Disease
- What is being tested?
- delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteSpain
- Study dates
- Sep 2011to Jun 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington's Disease
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.
Read more
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
- Being tested
- delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), Placebo
- Keywords
- Huntington's disease, cannabinoids
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboDrug
Placebo, One spray per day, up to a maximum of 12 sprays per day.
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Experimental | Not described Receives: Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious Adverse Events reported
Measured: 8 months
Changes in the UHDRs Score
UHDRS scale scores from the following perspectives: motor, cognitive, psychiatric and functional.
Measured: 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
Measured: 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.
Measured: On week 12 of each period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2011 (estimated)
- Study startSep 2011
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Huntington's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Collaborators
- GW Pharmaceuticals Ltd
- Responsible party
- Sponsor
- Investigators
- Justo García de Yébenes, Principal investigator, Hospital Universitario Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01502046
- Sponsor's protocol ID
- SAT-HD
- Other IDs
- 2010-024227-24
- Status last verified
- Jan 2013
- First submitted
- 29 Dec 2011
- Last updated
- 1 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27159993
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomized, Cross Over, Placebo Controlled Phase 2 Clinical Trial to Asses Neuroprotection by Cannabinoids in Huntington's Disease
- ClinicalTrials.gov ID
- NCT01502046
- Acronym / sponsor ID
- SAT-HD
- Conditions
- Huntington's Disease
- Keywords
- Huntington's disease, cannabinoids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Collaborators
- GW Pharmaceuticals Ltd
- Study start
- Sep 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 30 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sativex | Experimental | Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Sativex |
| PlaceboPlacebo, One spray per day, up to a maximum of 12 sprays per day. | Drug | Placebo |
Primary outcome
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.
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2013.
- Derived from this study: PubMed 27159993Lopez-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Justo García de Yébenes principal investigator
Hospital Universitario Ramon y Cajal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in people with Huntington's Disease, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious Adverse Events reported (time frame: 8 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01502046, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2013.