Dementia ModeratePhase 2NCT05612711
Dronabinol for Agitation in Dementia Crossover Trial
A Phase 2 study testing Dronabinol in people with Dementia Moderate and Dementia Severe, run by Ralph H. Johnson VA Medical Center at 1 site in United States.
Trial summary
The goal of this clinical trial is to study the effects of dronabinol in US Veterans with agitation related to moderate to severe dementia. The main goals of the study are: To evaluate the efficacy of dronabinol for the treatment of agitation in moderate to severe dementia compared to placebo To evaluate the safety of… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Dementia Moderate, Dementia Severe, Agitation,Psychomotor
- What is being tested?
- Dronabinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2023to Nov 2026
- 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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- US Veteran who is not pregnant or unable to become pregnant
- Diagnosis of Major Neurocognitive Disorder (aka dementia) of any type
- Functional Assessment Staging Test (FAST) score of 5 or higher
- Presence of clinically significant agitation and/or irritability with an NPI subscale score greater than or equal to 4
- If treated with cholinesterase inhibitors or memantine, dosage must be stable for 3 months, or if discontinued they may enroll after 1 month
- Must be able to swallow capsules
Show all 9Show fewer
- Must meet International Psychogeriatric Association's provisional definition of agitation in dementia.
- Must have decisional capacity to sign informed consent or have a legally authorized representative available to provide consent
- Must have an available study partner who spends at least 10 hours per week with the subject.
Who cannot join
- Psychotropic medication changes (i.e. concomitant antidepressants, antipsychotics) less than 1 month prior to study randomization
- Contraindications to dronabinol (hypersensitivity or allergy to any cannabinoid or sesame oil)
- Use of cannabinoids (including over the counter products such as "CBD" or medical cannabis) or other illicit drugs in the past 3 months
- History of psychotic symptoms due to another psychiatric illness other than dementia int he past 2 years.
- Unstable current psychiatric disorder or neurologic condition (i.e. unstable depression, bipolar disorder, epilepsy, etc.) other than agitation or psychosis due to dementia.
- Suicidal ideations in the past 3 months or attempts in the past year
Show all 9Show fewer
- Clinically significant delusions and/or hallucinations which are considered by the PI's to be a contraindication for dronabinol use
- Taking 1 or more medications which in the judgement of the PI's can be contraindicated with the use of dronabinol
- Unstable or uncontrolled medical conditions including cardiovascular system issues (i.e. angina, cardiac arrhythmias, recurrent syncope, hypertension, etc) as judged by the PI's.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ralph H. Johnson VA Health Care System
Charleston, South Carolina, 29401
About this study
Official title: Single-site, Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Dronabinol for the Treatment of Agitation in Outpatient With Dementia
The goal of this clinical trial is to study the effects of dronabinol in US Veterans with agitation related to moderate to severe dementia. The main goals of the study are:
- To evaluate the efficacy of dronabinol for the treatment of agitation in moderate to severe dementia compared to placebo
- To evaluate the safety of dronabinol in the treatment of agitation in moderate to severe dementia compared to placebo
Read more
Fifty (50) subjects will be given either dronabinol or placebo for 8 weeks. All subjects will then undergo a "washout" phase for 3 weeks, followed by the crossover intervention (i.e. subjects who received placebo during the first phase will receive dronabinol during the second phase, and vice versa). Thus, all participants will be taking dronabinol at some point during the study. During the study, subjects will undergo evaluations for:
- Agitation
- Cognitive changes
- Physical changes (i.e. labs, ekg, physical exam)
Read the detailed description
The investigators will conduct a phase IIa study to evaluate the efficacy and safety of dronabinol in the treatment of agitation related to dementia in the US Veteran population.
Specific Aim 1 - To evaluate the efficacy of dronabinol (target dose 5 mg bid) for the treatment of agitation in dementia.
Hypothesis: Dronabinol improves clinically significant agitation in moderate to severe dementia. Approach: The investigators will conduct a 6-week, double-blind, placebo-controlled, crossover, exploratory study of 50 Veterans suffering from moderate to severe dementia and clinically significant agitation with the Cohen Mansfield Agitation Inventory (CMAI) total score as the main outcome measure. Impact: The potential benefit of dronabinol in agitation will be evaluated.
Specific Aim 2 - To evaluate the safety of dronabinol in the treatment of agitation in moderate to severe dementia.
Hypothesis: Dronabinol is safe for the treatment of agitation in moderate to severe dementia. Approach: Outcomes of safety monitoring are to be measured by physical examination, vital signs with weight, adverse event reports, electrocardiogram, safety labs including complete metabolic panel (CMP), complete blood count (CBC), urinalysis (UA), and treatment compliance. Impact: The potential adverse effects of the 5 mg dose of dronabinol will be evaluated.
Exploratory Aims - The investigators will also evaluate the effect of dronabinol on neuropsychiatric symptoms, caregiver distress, cognition, weight, nutritional status, pain, and inflammation.
- Being tested
- Dronabinol
- Keywords
- Dementia, Agitation, Behavioral and Psychological Symptoms of Dementia
- Medical subject headings
- Psychomotor Agitation, Behavioral Symptoms, Dementia, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DronabinolDrug
Also called Marinol
All participants will take both dronabinol and placebo at different points in the study in this crossover design trial.
| Study group | Role | What they receive |
|---|---|---|
| Dronabinol First | Experimental | Participants will take Dronabinol 2.5 mg capsules twice daily for 1 week, followed by dronabinol 5 mg twice daily for 6 weeks, followed by dronabinol 2.5 mg twice daily for 1 week. They will then undergo a 3-week washout period, followed by placebo capsules twice daily for 8 weeks. Receives: Drug: Dronabinol |
| Placebo First | Experimental | Participants will take matching placebo capsules twice daily for 8 weeks, followed by a three week washout period. They will then begin taking dronabinol 2.5 mg capsules twice daily for 1 week, followed by dronabinol 5 mg twice daily for 6 weeks, followed by dronabinol 2.5 mg twice daily for 1 week. Receives: Drug: Dronabinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in agitation, Cohen Mansfield Agitation Inventory (CMAI)
A 29-item scale to assess 4 dimensions of agitation across a range of frequencies during the previous two weeks. Scores range from 29-203, where higher scores indicate greater agitation severity.
Measured: Baseline (0 weeks) to 18 weeks
Safety and tolerability, Treatment Emergent Adverse Events
We will compare the frequency of reported adverse events using Common Terminology Criteria for Adverse Events version 4.0
Measured: Baseline (0 weeks) to 18 weeks
Secondary outcomes (12)
Change in agitation, Neuropsychiatric Inventory (NPI)
This scale provides a comprehensive evaluation of neuropsychiatric symptoms in the previous month across 12 domains of behavior. Total scores range from 0-144, where higher scores reflect a greater level of neuropsychiatric symptom burden.
Measured: Baseline (0 weeks) to 18 weeks
Change in caregiver distress, Neuropsychiatric Inventory - Caregiver distress score
Caregiver distress is rated for each positive neuropsychiatric symptom domain on a scale of 0 (not distressing at all) to 5 (extremely distressing). Thus total scores range from 0-60 on for the 12 domains.
Measured: Baseline (0 weeks) to 18 weeks
Clinically perceptible effect of dronabinol on agitation, modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADAS-CGIC)
This modified version of the Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change assesses ites specific to agitation in Alzheimer's disease to produce a global rating of change in agitation and a measure of clinical significance. Scores range from 1 to 7 where 1 = marked improvement, 4 = no change, and 7 = marked worsening)
Measured: Baseline (0 weeks) to 18 weeks
Change in cognition, standardized Mini Mental Status Examination (sMMSE)
The standardized version of the original MMSE is a 30 point scale to measure global cognition, where lower scores indicate greater cognitive impairment.
Measured: Baseline (0 weeks) to 18 weeks
Change in cognition, Alzheimer's Disease Assessment Scale - Cognitive Section (ADAS-Cog)
This scale includes 11 items, 8 of which are performance based and 3 are ratings of language impairment. Scores range from 0-70, where higher scores indicate greater impairment. This scale will be administered to subjects scoring greater than or equal to 12 on the sMMSE.
Measured: Baseline (0 weeks) to 18 weeks
Change in cognition, Severe Impairment Battery
The severe impairment battery is a measure of cognition developed for the evaluation of patients whose dementia severity is such that they cannot complete conventional neuropsychological testing. It will be administered to anyone with an sMMSE score less than 12. Scores range from 0 to 133, where lower scores indicate greater impairment.
Measured: Baseline (0 weeks) to 18 weeks
Change in nutritional status, prealbumin
Assessed by changes in prealbumin (mg/dl)
Measured: Baseline (0 weeks) to 18 weeks
Change in nutritional status, weight
Assessed by changes in weight (kg)
Measured: Baseline (0 weeks) to 18 weeks
Change in pain, Pain Assessment in Advanced AD (PAIN-AD) scale
The PAIN-AD scale is a 5-item rater observed scale to measure pain in patients with dementia. Scores range from 0-10, where higher scores suggest a higher level of pain.
Measured: Baseline (0 weeks) to 18 weeks
Change in blood pressure
Blood pressure (mm Hg) will be monitored every 2 weeks
Measured: Baseline (0 weeks) to 18 weeks
Change in heart rate
Heart rate will be monitored in beats per minute (bpm) every 2 weeks to monitor safety.
Measured: Baseline (0 weeks) to 18 weeks
Change in QTc interval on Electrocardiogram (EKG)
EKGs will be monitored at each study visit to assess changes in QTc interval and monitor safety
Measured: Baseline (0 weeks) to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2022
- Study startNov 2023 (estimated)
- Primary completionNov 2025 (estimated)
- Study completionNov 2026 (estimated)
Why it stopped: Not funded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dementia ModerateStudies of the same condition, open and under way.
- 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
- Model description
- Eligible subjects will be randomization to either dronabinol or placebo (1:1 assignment ratio) for a total of 8 weeks (1 week of titration, followed by 6 weeks of treatment at target dose, followed by 1 week of taper). All subjects will then undergo a 3-week placebo washout phase, followed by the crossover intervention for 8 weeks.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ralph H. Johnson VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- JHSPH Center for Clinical Trials
- Responsible party
- Principal investigator, Jacobo Mintzer, MD, Ralph H. Johnson VA Medical Center
- Investigators
- Jacobo E Mintzer, MD, Principal investigator, Ralph H. Johnson VA Healthcare SystemJessica E Broadway, MD, Principal investigator, Ralph H. Johnson VA Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05612711
- Sponsor's protocol ID
- 1I01CX002671
- Status last verified
- Jul 2024
- First submitted
- 28 Oct 2022
- Last updated
- 5 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-site, Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Dronabinol for the Treatment of Agitation in Outpatient With Dementia
- ClinicalTrials.gov ID
- NCT05612711
- Acronym / sponsor ID
- 1I01CX002671
- Keywords
- Dementia, Agitation, Behavioral and Psychological Symptoms of Dementia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not funded
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ralph H. Johnson VA Medical CenterUS federal agency
- Collaborators
- JHSPH Center for Clinical Trials
- Study start
- Nov 2023 (estimated)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 10 Nov 2022 (actual)
- 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.
The goal of this clinical trial is to study the effects of dronabinol in US Veterans with agitation related to moderate to severe dementia. The main goals of the study are:
- To evaluate the efficacy of dronabinol for the treatment of agitation in moderate to severe dementia compared to placebo
- To evaluate the safety of dronabinol in the treatment of agitation in moderate to severe dementia compared to placebo
Fifty (50) subjects will be given either dronabinol or placebo for 8 weeks. All subjects will then undergo a "washout" phase for 3 weeks, followed by the crossover intervention (i.e. subjects who received placebo during the first phase will receive dronabinol during the second phase, and vice versa). Thus, all participants will be taking dronabinol at some point during the study. During the study, subjects will undergo evaluations for:
- Agitation
- Cognitive changes
- Physical changes (i.e. labs, ekg, physical exam)
Detailed description
The investigators will conduct a phase IIa study to evaluate the efficacy and safety of dronabinol in the treatment of agitation related to dementia in the US Veteran population.
Specific Aim 1 - To evaluate the efficacy of dronabinol (target dose 5 mg bid) for the treatment of agitation in dementia.
Hypothesis: Dronabinol improves clinically significant agitation in moderate to severe dementia. Approach: The investigators will conduct a 6-week, double-blind, placebo-controlled, crossover, exploratory study of 50 Veterans suffering from moderate to severe dementia and clinically significant agitation with the Cohen Mansfield Agitation Inventory (CMAI) total score as the main outcome measure. Impact: The potential benefit of dronabinol in agitation will be evaluated.
Specific Aim 2 - To evaluate the safety of dronabinol in the treatment of agitation in moderate to severe dementia.
Hypothesis: Dronabinol is safe for the treatment of agitation in moderate to severe dementia. Approach: Outcomes of safety monitoring are to be measured by physical examination, vital signs with weight, adverse event reports, electrocardiogram, safety labs including complete metabolic panel (CMP), complete blood count (CBC), urinalysis (UA), and treatment compliance. Impact: The potential adverse effects of the 5 mg dose of dronabinol will be evaluated.
Exploratory Aims - The investigators will also evaluate the effect of dronabinol on neuropsychiatric symptoms, caregiver distress, cognition, weight, nutritional status, pain, and inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Eligible subjects will be randomization to either dronabinol or placebo (1:1 assignment ratio) for a total of 8 weeks (1 week of titration, followed by 6 weeks of treatment at target dose, followed by 1 week of taper). All subjects will then undergo a 3-week placebo washout phase, followed by the crossover intervention for 8 weeks.
| Arm | Type | Receives |
|---|---|---|
| Dronabinol First | Experimental | Drug: DronabinolParticipants will take Dronabinol 2.5 mg capsules twice daily for 1 week, followed by dronabinol 5 mg twice daily for 6 weeks, followed by dronabinol 2.5 mg twice daily for 1 week. They will then undergo a 3-week washout period, followed by placebo capsules twice daily for 8 weeks. |
| Placebo First | Experimental | Drug: DronabinolParticipants will take matching placebo capsules twice daily for 8 weeks, followed by a three week washout period. They will then begin taking dronabinol 2.5 mg capsules twice daily for 1 week, followed by dronabinol 5 mg twice daily for 6 weeks, followed by dronabinol 2.5 mg twice daily for 1 week. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- US Veteran who is not pregnant or unable to become pregnant
- Diagnosis of Major Neurocognitive Disorder (aka dementia) of any type
- Functional Assessment Staging Test (FAST) score of 5 or higher
- Presence of clinically significant agitation and/or irritability with an NPI subscale score greater than or equal to 4
- If treated with cholinesterase inhibitors or memantine, dosage must be stable for 3 months, or if discontinued they may enroll after 1 month
Key exclusion criteria (9 listed)
- Psychotropic medication changes (i.e. concomitant antidepressants, antipsychotics) less than 1 month prior to study randomization
- Contraindications to dronabinol (hypersensitivity or allergy to any cannabinoid or sesame oil)
- Use of cannabinoids (including over the counter products such as "CBD" or medical cannabis) or other illicit drugs in the past 3 months
- History of psychotic symptoms due to another psychiatric illness other than dementia int he past 2 years.
- Unstable current psychiatric disorder or neurologic condition (i.e. unstable depression, bipolar disorder, epilepsy, etc.) other than agitation or psychosis due to dementia.
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 |
|---|---|---|
| DronabinolAlso: MarinolAll participants will take both dronabinol and placebo at different points in the study in this crossover design trial. | Drug | Dronabinol First, Placebo First |
Primary outcome
Change in agitation, Cohen Mansfield Agitation Inventory (CMAI)
Time frame: Baseline (0 weeks) to 18 weeks
A 29-item scale to assess 4 dimensions of agitation across a range of frequencies during the previous two weeks. Scores range from 29-203, where higher scores indicate greater agitation severity.
Safety and tolerability, Treatment Emergent Adverse Events
Time frame: Baseline (0 weeks) to 18 weeks
We will compare the frequency of reported adverse events using Common Terminology Criteria for Adverse Events version 4.0
12 secondary outcomes
Change in agitation, Neuropsychiatric Inventory (NPI)
Time frame: Baseline (0 weeks) to 18 weeks
Change in caregiver distress, Neuropsychiatric Inventory - Caregiver distress score
Time frame: Baseline (0 weeks) to 18 weeks
Clinically perceptible effect of dronabinol on agitation, modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADAS-CGIC)
Time frame: Baseline (0 weeks) to 18 weeks
Change in cognition, standardized Mini Mental Status Examination (sMMSE)
Time frame: Baseline (0 weeks) to 18 weeks
Change in cognition, Alzheimer's Disease Assessment Scale - Cognitive Section (ADAS-Cog)
Time frame: Baseline (0 weeks) to 18 weeks
Change in cognition, Severe Impairment Battery
Time frame: Baseline (0 weeks) to 18 weeks
Change in nutritional status, prealbumin
Time frame: Baseline (0 weeks) to 18 weeks
Change in nutritional status, weight
Time frame: Baseline (0 weeks) to 18 weeks
Change in pain, Pain Assessment in Advanced AD (PAIN-AD) scale
Time frame: Baseline (0 weeks) to 18 weeks
Change in blood pressure
Time frame: Baseline (0 weeks) to 18 weeks
Change in heart rate
Time frame: Baseline (0 weeks) to 18 weeks
Change in QTc interval on Electrocardiogram (EKG)
Time frame: Baseline (0 weeks) to 18 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2024.
- Individual participant dataSharing planned: No
Related trials for Dementia Moderate
Active, not recruiting
Health enSuite Caregivers: an App-based Treatment for Distressed Caregivers of Persons With Moderate Dementia
Caregiver Burnout
Not yet recruiting
A Mobile Informatics Solution to Assist Caregivers in Care Coordination and Monitoring Social Engagement
Memory Disorders, Mild Cognitive Impairment
Not yet recruitingPhase 3
Tricaprilin Phase 3 ALTER-AD (Alternative-Alzheimer Disease) Study
Alzheimer Disease
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease
Alzheimer's Disease
Active, not recruitingPhase 2/3
Effect of 10 mg Xanamem on Dementia Due to Alzheimer's Disease
Dementia Moderate, Dementia, Mild
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.
Jacobo E Mintzer, MD principal investigator
Ralph H. Johnson VA Healthcare System
Jessica E Broadway, MD principal investigator
Ralph H. Johnson VA Healthcare System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dronabinol in people with Dementia Moderate and Dementia Severe, run by Ralph H. Johnson VA Medical Center at 1 site in United States.
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 9 inclusion and 9 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: withdrawn, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 was withdrawn before enrolling participants, so there are no results.
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?
Change in agitation, Cohen Mansfield Agitation Inventory (CMAI) (time frame: Baseline (0 weeks) to 18 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jul 2024.