Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease (AD) (THC-AD) (THC-AD)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02792257|
Recruitment Status : Recruiting
First Posted : June 7, 2016
Last Update Posted : July 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease||Drug: Dronabinol (Marinol®) Drug: Placebo||Phase 2|
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging, affecting an estimated 5.2 million Americans and predicted to increase to 13.8 million by 2050. AD affects both cognition and emotion. Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course with > 97% of AD patients having at least one symptom reported on the Neuropsychiatric Inventory (NPI).
One of the most troubling of these symptoms is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. In community-based samples, Agit-AD is common. Agit-AD is associated with greater caregiver burden and shorter time to institutionalization, and there is a particularly acute need for interventions for severe Agit-AD in advanced dementia.
While there are currently no FDA approved medications for Agit-AD, psychotropic medications are widely prescribed "off-label" to treat Agit-AD. The most commonly used classes of medications prescribed for "off-label" treatment are antipsychotics and antidepressants. The evidence to date for efficacy remains mixed. Antipsychotics appear to have some degree of efficacy, but the effects are not highly replicable and their use is associated with increased mortality in elderly patients with dementia. Antidepressants (particularly selective serotonin reuptake inhibitors, (SSRI)s) appear to have fewer and less severe adverse effects compared to antipsychotics, as well as no known mortality risks, but are not without limitation. Therefore, exploration of alternative treatments for Agit-AD, particularly severe cases, is timely and warranted.
Dronabinol (Marinol®) is FDA-approved for the treatment of anorexia/weight loss in AIDS and for nausea/emesis associated with chemotherapy, which is now being used off-label for Agit-AD. Dronabinol is a synthetic oral formulation of delta-9-tetrahydrocannabinol (THC), a psychoactive constituent of the cannabis plant that acts as a partial agonist at the Type 1 (CB1) and Type 2 (CB2) endocannabinoid receptors. This pharmacology is appropriate for targeting Agit-AD because CB1 receptor agonism can produce anxiolytic and antidepressant effects and CB2 receptor agonism can be anti-inflammatory.
The mechanism by which dronabinol exerts its effects on agitation and aggression in patients with dementia may occur through its action at the CB1 and/or the CB2 receptor. Agonists at the CB1 receptor in the brain improve anxiety and depression in humans as well as animal models. Dronabinol is an effective agonist at the CB1 receptor, which is generally specific to neurons and localized predominantly on the presynaptic terminal where it inhibits glutamatergic, dopaminergic and other neurotransmitter release. The CB1 receptor effects has been observed to mediate the observed anxiolytic and antidepressant effects of THC. Dronabinol is also an agonist at CB2, a potent anti-inflammatory receptor localized on activated microglia. Patients with AD have increased central and peripheral inflammation, likely as a result of the accumulation of beta-amyloid. Increased inflammation may have a number of behavioral effects that could drive the agitation and aggression in dementia patients. Dronabinol's effects at the CB2 receptor therefore could also produce changes in behavior in AD patients by reducing inflammation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||160 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Pilot Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease (AD) (THC-AD)|
|Actual Study Start Date :||March 1, 2017|
|Estimated Primary Completion Date :||May 2022|
|Estimated Study Completion Date :||May 2022|
Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3.
Drug: Dronabinol (Marinol®)
5mg - 10mg daily dose
Placebo Comparator: Placebo
Placebo medication will be administered twice daily.
- Symptoms of agitation as measured by the Pittsburgh Agitation Scale [ Time Frame: 3-weeks ]Scale will be administered weekly
- Symptoms of agitation as measured by the Neuropsychiatric Inventory, Clinician Version [ Time Frame: 3-weeks ]Scale will be administered weekly
- Adverse events in Dronabinol treatment as compared to placebo [ Time Frame: 3-weeks ]All Adverse Events (AE) s occurring after randomization and during the 3-week treatment period, regardless of adherence to study treatment, will be recorded at all contacts.
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): NCT02792257
|Contact: John Outen, M.S.||email@example.com|
|Contact: Eleanor Ash, B.A.||firstname.lastname@example.org|
|United States, Florida|
|Miami Jewish Health||Recruiting|
|Miami, Florida, United States, 33137|
|Contact: Maria Isesalaya, MBA, BS 305-751-8626 ext 64108 email@example.com|
|Contact: Ricardo Castaneda, PharmD, CCRC 305-751-8626 ext 64199 firstname.lastname@example.org|
|Principal Investigator: Marc Agronin, M.D.|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: John Outen, M.S. 410-550-7385 email@example.com|
|Principal Investigator: Paul Rosenberg, MD|
|United States, Massachusetts|
|Belmont, Massachusetts, United States, 02478|
|Contact: Eleanor Ash, B.A. 617-855-2589 firstname.lastname@example.org|
|Contact: Leah Cohen, B.A. Lcohen@mclean.harvard.edu|
|Principal Investigator: Brent P Forester, MD, MSc|
|Principal Investigator:||Paul Rosenberg||Johns Hopkins University|
|Principal Investigator:||Brent Forester||Mclean Hospital|