Clinical trial NCT01302340: Delta-THC in Behavioral Disturbances in Dementia
Official title: Two Phase, Repeated Crossover Study With Dose Escalation on Delta(9)-Tetrahydrocannabinol (Delta-THC) in Behavioral Disturbances in Dementia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dementia
Keywords: Dementia
Alzheimer
Cannabis
THC
Behavioral Disturbances
Neuropsychiatric Inventory
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: European Union
First posted: 2011-02-24
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Neuropsychiatric Inventory (NPI)
timeFrame: At day 3 and 10 during treatment blocks and after 1 month, 3 months and 6 months in the open label extension phase
Secondary outcomes:
measure: Cohen-Mansfield Agitation Inventory (CMAI)
timeFrame: 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
measure: Zarit Burden Scale (ZBS)
timeFrame: At days 3 and 10 during treatment blocks and months 1, 3 and 6 during extension phase
measure: Visual Analogue Scale (VAS) Bowdle for feeling high
timeFrame: 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
measure: Gait rite®
timeFrame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
measure: Sway Star®
timeFrame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
measure: Time up and go
timeFrame: 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
measure: Tinetti Balance Assessment Tool
timeFrame: 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
measure: pharmacogenetics
timeFrame: day 1
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
state: Gelderland
city: Venray
country: Netherlands
facility: Vincent van Gogh Institute for Psychiatry, department of Elderly
state: Limburg
Study officials:
affiliation: Radboud University Medical Center
name: Marcel Olde Rikkert, prof MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.