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Delta-THC in Behavioral Disturbances in Dementia

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ClinicalTrials.gov Identifier: NCT01302340
Recruitment Status : Completed
First Posted : February 24, 2011
Last Update Posted : January 22, 2014
Sponsor:
Collaborator:
European Union
Information provided by (Responsible Party):
Marcel Olde Rikkert, Radboud University Medical Center

Study Description
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Brief Summary:
Dementia is a common chronic condition, with predicted increasing prevalence. Nearly all patients with dementia will experience neuropsychiatric symptoms (NPS). This causes significant burden for the individual patients and their caregivers. Current treatment has only modest efficacy and important side-effects. Formulations with Δ9-tetrahydrocannabinol (THC), the psycho-active compound of cannabis, are currently being registered for spasms in multiple sclerosis and other diseases, and may have beneficial effects on NPS.

Condition or disease Intervention/treatment Phase
Dementia Drug: Delta-THC Drug: placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Two Phase, Repeated Crossover Study With Dose Escalation on Delta(9)-Tetrahydrocannabinol (Delta-THC) in Behavioral Disturbances in Dementia
Study Start Date : September 2011
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dementia

Arms and Interventions
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Arm Intervention/treatment
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)
 Drug: Delta-THC
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:
  • Namisol
  • Cannabis
  • ECP002A

Drug: Delta-THC
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:
  • Namisol
  • Cannabis
  • ECP002A
Placebo Comparator: placebo
Placebo will be administered twice daily during three consecutive days per treatment block.
 Drug: placebo
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 Name: Placebo Namisol


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    Improvement in behavior compared to placebo is measured with the NPI, which is the standard measure of Neuro Psychiatric Symptoms in most clinical trials.


Secondary Outcome Measures :
  1. 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 ]
    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

  2. Zarit Burden Scale (ZBS) [ Time Frame: At days 3 and 10 during treatment blocks and months 1, 3 and 6 during extension phase ]
    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.

  3. 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 ]
    severity and duration of feeling high episodes

  4. Gait rite® [ Time Frame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase ]
    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.

  5. Sway Star® [ Time Frame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase ]
    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.

  6. 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 ]
    Improvement and/or safety compared to placebo and during long term treatment on balance and mobility in elderly patients.

  7. 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 ]
    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.

  8. pharmacogenetics [ Time Frame: day 1 ]

    The following polymorphisms will be genotyped:

    • CYP2C9*2
    • CYP2C9*3
    • CYP2C19*2
    • CYP2C19*3
    • CYP2C19*17

    To investigate the role of CYP2C9 and CYP2C19 genetic polymorphisms in the interindividual variation in pharmacokinetics, efficacy and adverse events of THC.



Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

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): NCT01302340


Locations
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Netherlands
Radboud university medical center
Nijmegen, Gelderland, Netherlands, 6525EX
Vincent van Gogh Institute for Psychiatry, department of Elderly
Venray, Limburg, Netherlands, 5803
Sponsors and Collaborators
Radboud University Medical Center
European Union
Investigators
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Principal Investigator: Marcel Olde Rikkert, prof MD Radboud University Medical Center
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Marcel Olde Rikkert, Prof. dr., Radboud University Medical Center
ClinicalTrials.gov Identifier: NCT01302340    
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 )
First Posted: February 24, 2011    Key Record Dates
Last Update Posted: January 22, 2014
Last Verified: January 2014
Keywords provided by Marcel Olde Rikkert, Radboud University Medical Center:
Dementia
Alzheimer
Cannabis
 THC
Behavioral Disturbances
Neuropsychiatric Inventory
Additional relevant MeSH terms:
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Dementia
Problem Behavior
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Behavioral Symptoms
Dronabinol
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
Hormones, Hormone Substitutes, and Hormone Antagonists