Clinical trial NCT01608217: Delta-THC in Dementia
Official title: Efficacy and Safety of Delta-9-tetrahydrocannabinol (∆9-THC) in Behavioural Disturbances and Pain in Dementia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Behavioural Disturbances
Pain
Dementia
Alzheimer's Dementia
Vascular Dementia
Keywords: Behavioural disturbances
Pain
Dementia
Alzheimer's dementia
Vascular dementia
THC
Cannabis
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Health Valley, Netherlands
First posted: 2012-05-31
Enrollment: 50
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase II, randomized, placebo-controlled, double-blind, parallel-group, multicentre study to the efficacy and safety of low dose delta-9-THC in behavioural disturbances and pain in patients with mild to severe dementia, when added to an analgesic treatment with acetaminophen.

It is hypothesized that Namisol® will lead to more behavioural disturbances than placebo, when added to an analgesic treatment with acetaminophen, and as measured by a change in Neuropsychiatric Inventory (NPI) score, after a three week treatment period.

It is expected that this will be due, primarily, to psychoactive effects of Namisol® and secondary to a reduction in pain sensation (as measured with VRS and PACSLAC-D). It is expected that a reduction in NPS will positively affect quality of life and lead to better functioning in daily living.

Detailed description: There is a high prevalence of behavioural disturbances (NPS) in persons with dementia. Persistent pain complaints can be a cause of NPS. Unfortunately, there is a lack of appropriate drugs for treating both these problems. This and positive suggestions from preliminary clinical studies with THC on NPS and directly fuel the study presented here.

This will be a phase II study in which the efficacy and safety of Namisol® (a tablet with THC) on behavioural disturbances, such as agitation, aggression and motor disturbances in dementia patients will be evaluated.

Secondary study objectives are :

2. To evaluate the efficacy of Namisol® on other secondary outcome measures, such as quality of life and functioning in daily activities.

3. To evaluate safety of Namisol® as assessed with physical examination, effects on cognitive functioning and adverse event monitoring.

4. For the subgroup of subjects suffering from pain: to evaluate the efficacy of Namisol® pain intensity

It is hypothesized that Namisol® will lead to more reduction in behavioural disturbances than placebo, when added to an analgesic treatment with acetaminophen, and as measured by a change in Neuropsychiatric Inventory (NPI) score, after a three week treatment period. It is expected that this will be due, primarily, to psychoactive effects of Namisol® and secondary to a reduction in pain sensation (as measured with VRS and PACSLAC-D). It is expected that a reduction in NPS will positively affect quality of life and lead to better functioning in daily living

This is a randomized placebo-controlled double-blind parallel-group multicentre study.

Subjects who appear to fulfill the eligibility criteria are informed about the study. After signing informed consent by the subject and/or caregiver, a screening visit will take place. Subjects who are eligible for participation enter a wash-out period, for discontinuation of their own analgesic medication (if applicable). Subjects will be randomly allocated to receive one of the two interventions (Namisol® 1.5 mg + acetaminophen 1000 mg three times daily, or placebo + acetaminophen 1000 mg three times daily) for a double-blind intervention period of three weeks. After two weeks the primary outcome measure (NPI) is assessed by a telephone interview with the caregiver. Subjects visit the site twice (at baseline and after three weeks treatment) for assessments of the outcome parameters, including the NPI. For the purpose of compliance and safety, there will be a weekly phone call, performed by the researcher. After completion of this period subject's own analgesic treatment will be restarted (if applicable). After a follow up phase of two weeks, the subject is contacted by telephone for assessment of adverse events.

Eligibility criteria: Inclusion Criteria:

* Subject has possible or probable dementia, type Alzheimer, vascular or mixed type dementia, according to the criteria of NINCDS-ADRDA/NINCDS-AIREN or based on an expert panel decision.
* Clinical Dementia Rating (CDR) score 1 to 3 (mild to severe dementia).
* Age ≥ 40 years.
* Clinically relevant behavioral disturbances existing at least one month prior to screening, defined as a score of ≥ 10 on the NPI, including presence of the domain agitation/aggression or motor disturbance.
* Women should be in the postmenopausal phase.
* Availability of an informal or formal caregiver, being in touch with the subject at least twice a week.
* Informed consent by the subject and subject's informal caregiver.
* If applicable: subject is willing to stop his/her own pain medication, for the duration of the study.

Exclusion criteria:

* Dementia other than AD, VaD or AD/VaD
* Major psychiatric disorder such as: major depression according to DSM IV within 6 months prior to randomization, history of psychosis or mania, current hallucinations and/or delirium, current suicidal ideation or major anxiety disorder.
* History of, or current drug abuse.
* Current alcohol abuse or unwillingness to use no more than 2 alcoholic consumptions daily or raised gamma-glutamine transpeptidase and alkaline phosphatase .
* Clinical or biochemical evidence of liver disease (ALT or AST ≥ twice the upper limit of normal) or known allergy to acetaminophen.
* Severe (and/or unstable) concomitant or intercurrent illness, such as seizure, arrhythmias requiring other drugs than a beta blocker or digoxin (except sinus arrhythmia and atrial fibrillation), unstable angina pectoris, heart failure NYHA III or IV, and severe concomitant illness that requires treatment changes.
* Known or suspected sensitivity to cannabinoids.
* Lactosis intolerance.
* Frequent falling due to orthostatic hypotension.
* Use of tricyclic antidepressants (TCA), fluoxetine and/or carbamazepine.
* Changes in dosage of antipsychotics, benzodiazepines or cholinesterase inhibitors within 2 weeks prior to intervention.
* Participation in any other study other than the descriptive 'Parelsnoer' study.

Primary outcomes:
measure: Neuropsychiatric Inventory (NPI)
timeFrame: Screening, baseline, T= 2 weeks (by telephone interview) and T=3 weeks
Secondary outcomes:
measure: Pain Assessment Checklist for Seniors with Limited Ability to Communicate Dutch version (PACSLAC-D)
timeFrame: baseline (T = 0) and T= 3 weeks
measure: Caregiver Clinical Global Impression of Change (CCGIC)
timeFrame: baseline (T=0), T= 2 wks (by telephone interview) and T=3 wks
measure: Cohen-Mansfield Agitation Inventory (CMAI)
timeFrame: baseline (T=0) and T= 3 weeks
measure: Quality of Life-Alzheimer's Disease Scale (QoL-AD)
timeFrame: baseline (T=0) and T= 3 weeks
measure: Barthel Index
timeFrame: baseline (T=0) and T = 3 weeks
measure: Paired Associates Learning test Wechsler Memory Scale Revised(PAL WMS-R)
timeFrame: baseline (T = 0) and T = 3 weeks
measure: Safety assessments
timeFrame: screening, baseline (T=0), T= 3 weeks. AE and compliance during telephone calls at T= 1week, T= 2 weeks and T= 5 weeks (follow up phone call)
measure: Verbal Rating Scale (VRS)
timeFrame: screening, baseline, T= 3 weeks, follow up (T= 5 weeks) and daily in a medication diary
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud university medical center, department of Geriatrics
state: Gelderland
city: Venlo
country: Netherlands
facility: Vincent van Gogh Institute for Psychiatry, department of Elderly
state: Limburg
Study officials:
affiliation: Radboud University Medical Center Nijmegen
name: Marcel Olde Rikkert, prof. dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Vincent van Gogh voor Geestelijke Gezondheidszorg
name: Willem Verhoeven, Prof. dr.
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.