- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01302340
Delta-THC in Behavioral Disturbances in Dementia
Two Phase, Repeated Crossover Study With Dose Escalation on Delta(9)-Tetrahydrocannabinol (Delta-THC) in Behavioral Disturbances in Dementia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Design Phase II pilot study, multi-center, repeated cross-over, double blinded randomized trial. The study consists of two weeks baseline measurements to assure that the neuropsychiatric symptoms are stable and six successive treatment blocks of 2 weeks. Each treatment block lasts for two weeks and contains two double-blinded drug periods, each lasting three days of oral THC or placebo, separated by four day washout periods. After three treatment blocks (period A), the dosage of active treatment was increased for the latter three treatment blocks (period B). After the two treatment periods, subjects will proceed to the extension phase if applicable.
Study centers The department of Geriatrics from Radboud University Nijmegen Medical Centre and the department of Elderly from Vincent van Gogh voor Geestelijke Gezondheidszorg Venray (VVG) will participate in this multi center study.
Participants 20 subjects with dementia and NPS. Intervention Namisol® in doses of twice daily 0,75 mg tablet (period A) and twice daily 1.5 mg (period B) THC oral tablets. Placebo of twice daily 0,75 mg and twice daily 1.5 mg oral tablets Outcome measures Primary outcome is NPI score, secondary CMAI, Zarit Burden scale. Other outcomes include vital signs, side-effects, physical exam, mobility and pharmacogenetics.
Visits This study will be assessed fully ambulatory, starting with a 5 hour clinical visit on day 1 and 8 of block 1 and a phone call on day 2 and 9 for assessment of Adverse Events. Furthermore, the research physician will conduct a weekly home visit weekly during the crossover phase for assessment of , among others, the primary outcome measure. These visits will all be repeated in period B of the crossover phase.
During the 6 month open label extension phase, subjects will visit the clinic three times.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Gelderland
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Nijmegen, Gelderland, Netherlands, 6525EX
- Radboud University Medical Center
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Limburg
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Venray, Limburg, Netherlands, 5803
- Vincent van Gogh Institute for Psychiatry, department of Elderly
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of Alzheimer's Disease (AD), Vascular Dementia (VD) or mixed, according to the criteria of NINCDS-ADRDA or NINCDS-AIREN
- Clinical Dementia Rating score between 0.5 and 3
- NPS symptoms, with at least agitation or aggression
Exclusion Criteria:
- Diagnosis of Lewy Body Dementia (LBD) or Fronto-Temporal Dementia (FTD)
- Major psychiatric disorder
- Severe concomitant illness, seizure, arrhythmias (except sinus arrhythmia and atrial fibrillation), heart failure New York Heart Association (NYHA) class III or IV
- Tri Cyclic Antidepressives (TCA) or opioids used within 30 days before randomization till the end of the study
- Changes in dosage of antidepressives within 6 weeks before randomization and during study, and changes in dosage antipsychotics or benzodiazepines within 2 weeks prior to randomization and during study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Delta-THC
THC will be administered twice daily during three consecutive days per treatment block(0.75 or 1.5 mg twice daily)
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Active treatment consists of THC in tablet form.
Patients receive 0.75 mg THC twice daily during the first three treatment blocks (period A) and 1.5 mg THC twice daily during the latter three treatment blocks (period B).
Placebo treatment consists of two tablets daily and is matched to the active treatment for taste, color and size.
Study medication will be administered at 10 a.m. and 4 p.m., by the primary caregiver.
These time points are chosen because NPS often occur later on the day, when fatigue and external signals build up to the stress and result in NPS.
The order of administration of THC and placebo (1:1) will be determined by randomization per block: THC followed by placebo or placebo followed by THC.
Other Names:
In case either 2 times daily 1 tablet 0,75mg or 2 times daily 1 tablet 1.5mg Delta-THC appeared to be efficacious for a particular patient, this patient can continue the effective dose of delta-THC in an open label extension phase during 6 months.
Other Names:
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Placebo Comparator: placebo
Placebo will be administered twice daily during three consecutive days per treatment block.
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Active treatment consists of THC in tablet form.
Patients receive 0.75 mg THC twice daily during the first three treatment blocks (period A) and 1.5 mg THC twice daily during the latter three treatment blocks (period B).
Placebo treatment consists of two tablets daily and is matched to the active treatment for taste, color and size.
Study medication will be administered at 10 a.m. and 4 p.m., by the primary caregiver.
These time points are chosen because NPS often occur later on the day, when fatigue and external signals build up to the stress and result in NPS.
The order of administration of THC and placebo (1:1) will be determined by randomization per block: THC followed by placebo or placebo followed by THC.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Neuropsychiatric Inventory (NPI)
Time Frame: At day 3 and 10 during treatment blocks and after 1 month, 3 months and 6 months in the open label extension phase
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Improvement in behavior compared to placebo is measured with the NPI, which is the standard measure of Neuro Psychiatric Symptoms in most clinical trials.
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At day 3 and 10 during treatment blocks and after 1 month, 3 months and 6 months in the open label extension phase
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cohen-Mansfield Agitation Inventory (CMAI)
Time Frame: At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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Improvement in agitation compared to placebo and during long term treatment is measured with CMAI.
It is useful in determining fluctuations in behaviors and emotional states in Alzheimer's Disease
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At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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Zarit Burden Scale (ZBS)
Time Frame: At days 3 and 10 during treatment blocks and months 1, 3 and 6 during extension phase
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Reducing caregiver stress compared to placebo and during long term treatment by focusing on the patients' behavior compared to Zarit burden interviews with the caregiver.
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At days 3 and 10 during treatment blocks and months 1, 3 and 6 during extension phase
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Visual Analogue Scale (VAS) Bowdle for feeling high
Time Frame: At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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severity and duration of feeling high episodes
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At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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Gait rite®
Time Frame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
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Improvement and/or safety compared to placebo and during long term treatment on balance and mobility.
It is a non invasive and highly feasible mobility assessment.
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At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
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Sway Star®
Time Frame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
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Improvement and/or safety compared to placebo and during long term treatment on balance and mobility.
It is a non invasive and highly feasible mobility assessments.
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At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
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Time up and go
Time Frame: At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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Improvement and/or safety compared to placebo and during long term treatment on balance and mobility in elderly patients.
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At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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Tinetti Balance Assessment Tool
Time Frame: At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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Improvement and/or safety compared to placebo and during long term treatment on balance and mobility in elderly patients.
It is a performance-oriented assessment of mobility problems in elderly patients.
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At days 1, 3, 8, and 10 during treatment blocks 1 and 4 and weekly during treatment blocks 2, 3, 5 and 6 and months 1, 3, 6 and 6 during extension phase
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pharmacogenetics
Time Frame: day 1
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The following polymorphisms will be genotyped:
To investigate the role of CYP2C9 and CYP2C19 genetic polymorphisms in the interindividual variation in pharmacokinetics, efficacy and adverse events of THC. |
day 1
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Marcel Olde Rikkert, prof MD, Radboud University Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Problem Behavior
- Dementia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Psychotropic Drugs
- Hallucinogens
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Dronabinol
Other Study ID Numbers
- GER001-02-01
- 2009-019329 (Other Grant/Funding Number: Province of Gelderland&Overijssel)
- 2010-024577-39 (EudraCT Number)
- Supplies Investigational Drug (Other Grant/Funding Number: Echo pharmaceuticals)
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