Ignite Creation Date:
2024-05-06 @ 8:41 AM
Last Modification Date:
2024-10-26 @ 12:03 PM
Study NCT ID:
NCT02792257
Status:
COMPLETED
Last Update Posted:
2024-06-07
First Post:
2016-05-26
Brief Title:
Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimers Disease
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
Pilot Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimers Disease
Status:
COMPLETED
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
THC-AD
Brief Summary:
Alzheimers disease AD is the most prevalent neurodegenerative disease of aging 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 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 There is a great need for better interventions that target Agit-AD a major source of patient disability as well as caregiver burden and stress particularly in the case of moderate to severe agitation This pilot trial could open the door to re-purposing Dronabinol Marinol as a novel and safe treatment for Agit-AD with significant public health impact
Detailed Description:
Alzheimers disease AD is the most prevalent neurodegenerative disease of aging affecting an estimated 52 million Americans and predicted to increase to 138 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 its use is associated with increased mortality in elderly patients with dementia Antidepressants particularly selective serotonin reuptake inhibitors SSRIs 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 anorexiaweight loss in AIDS and for nauseaemesis 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 andor 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 Dronabinols effects at the CB2 receptor therefore could also produce changes in behavior in AD patients by reducing inflammation
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 its use is associated with increased mortality in elderly patients with dementia Antidepressants particularly selective serotonin reuptake inhibitors SSRIs 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 anorexiaweight loss in AIDS and for nauseaemesis 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 andor 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 Dronabinols effects at the CB2 receptor therefore could also produce changes in behavior in AD patients by reducing inflammation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01AG050515 | NIH | None | httpsreporternihgovquickSearchR01AG050515 |