DementiaPhase 2NCT01302340
Delta-THC in Behavioral Disturbances in Dementia
A Phase 2 study testing Delta-THC in people with Dementia, run by Radboud University Medical Center at 2 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dementia
- What is being tested?
- Delta-THC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 2 sitesNetherlands
- Study dates
- Sep 2011to Dec 2013
- 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
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Radboud university medical center
Nijmegen, Gelderland, 6525EX
Vincent van Gogh Institute for Psychiatry, department of Elderly
Venray, Limburg, 5803
About this study
Official title: Two Phase, Repeated Crossover Study With Dose Escalation on Delta(9)-Tetrahydrocannabinol (Delta-THC) in Behavioral Disturbances in Dementia
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.
Read the 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.
- Conditions
- Dementia
- Being tested
- Delta-THC, placebo
- Keywords
- Dementia, Alzheimer, Cannabis, THC, Behavioral Disturbances, Neuropsychiatric Inventory
- Medical subject headings
- Dementia, Marijuana Abuse, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delta-THCDrug
Also called Namisol, Cannabis, ECP002A
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.
placeboDrug
Also called Placebo Namisol
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.
Delta-THCDrug
Also called Namisol, Cannabis, ECP002A
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.
| Study group | Role | What they receive |
|---|---|---|
| Delta-THC | Active comparator | THC will be administered twice daily during three consecutive days per treatment block(0.75 or 1.5 mg twice daily) Receives: Drug: Delta-THC |
| placebo | Placebo comparator | Placebo will be administered twice daily during three consecutive days per treatment block. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychiatric Inventory (NPI)
Improvement in behavior compared to placebo is measured with the NPI, which is the standard measure of Neuro Psychiatric Symptoms in most clinical trials.
Measured: 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 (8)
Cohen-Mansfield Agitation Inventory (CMAI)
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
Measured: 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
Zarit Burden Scale (ZBS)
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.
Measured: At days 3 and 10 during treatment blocks and months 1, 3 and 6 during extension phase
Visual Analogue Scale (VAS) Bowdle for feeling high
severity and duration of feeling high episodes
Measured: 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
Gait rite®
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.
Measured: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
Sway Star®
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.
Measured: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
Time up and go
Improvement and/or safety compared to placebo and during long term treatment on balance and mobility in elderly patients.
Measured: 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
Tinetti Balance Assessment Tool
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.
Measured: 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
pharmacogenetics
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.
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2011 (estimated)
- Study startSep 2011
- Primary completionDec 2013
- Study completionDec 2013
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 DementiaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- European Union
- Responsible party
- Principal investigator, Marcel Olde Rikkert, Radboud University Medical Center
- Investigators
- Marcel Olde Rikkert, prof MD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01302340
- Sponsor's protocol ID
- GER001-02-01
- Other IDs
- 2009-019329, 2010-024577-39, Supplies Investigational Drug, 2009
- Status last verified
- Jan 2014
- First submitted
- 10 Feb 2011
- Last updated
- 22 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34532852
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Two Phase, Repeated Crossover Study With Dose Escalation on Delta(9)-Tetrahydrocannabinol (Delta-THC) in Behavioral Disturbances in Dementia
- ClinicalTrials.gov ID
- NCT01302340
- Acronym / sponsor ID
- GER001-02-01
- Conditions
- Dementia
- Keywords
- Dementia, Alzheimer, Cannabis, THC, Behavioral Disturbances, Neuropsychiatric Inventory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- European Union
- Study start
- Sep 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 24 Feb 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Delta-THC | Active comparator | Drug: Delta-THCTHC will be administered twice daily during three consecutive days per treatment block(0.75 or 1.5 mg twice daily) |
| placebo | Placebo comparator | Drug: placeboPlacebo will be administered twice daily during three consecutive days per treatment block. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
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-THCAlso: Namisol, Cannabis, ECP002AActive 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. | Drug | Delta-THC |
| placeboAlso: Placebo NamisolActive 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. | Drug | placebo |
| Delta-THCAlso: Namisol, Cannabis, ECP002AIn 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. | Drug | Delta-THC |
Primary outcome
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.
8 secondary outcomes
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
Zarit Burden Scale (ZBS)
Time frame: At days 3 and 10 during treatment blocks and months 1, 3 and 6 during extension phase
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
Gait rite®
Time frame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
Sway Star®
Time frame: At days 1 and 8 during blocks 1 and 4 and at 1, 3 and 6 months during extension phase
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
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
pharmacogenetics
Time frame: day 1
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 22 Jan 2014.
- Derived from this study: PubMed 34532852Bosnjak 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.
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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.
Marcel Olde Rikkert, prof MD principal investigator
Radboud University Medical Center
2 sites 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-THC in people with Dementia, run by Radboud University Medical Center at 2 sites in Netherlands.
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 3 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 22 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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?
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). 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 NCT01302340, 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 22 Jan 2014.