THC-Based Medication for Agitation in Alzheimer's

(CALMA Trial)

Recruiting at35 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: IGC Pharma, LLC

Disqualifiers: Seizures, Schizophrenia, Bipolar, Uncontrolled hypertension, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a natural THC-based medicine called IGC-AD1, given in small doses regularly. It targets people aged 60 and above with Alzheimer's-related dementia who have been experiencing agitation. The THC in the medicine helps reduce agitation by interacting with brain signals. The most recent trial reported significant improvement in agitation using nabilone.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, any medications for behavioral symptoms should have been consistent for at least 3 months before screening, with only minor dose changes allowed.

What data supports the effectiveness of the drug IGC-AD1 for agitation in Alzheimer's patients?

Research suggests that cannabinoids, like THC, may help reduce agitation in Alzheimer's patients by calming anxiety and improving mood. A study on dronabinol, a synthetic form of THC, is exploring its safety and effectiveness for this purpose, and similar studies on nabilone, another synthetic cannabinoid, indicate potential benefits for agitation, pain, and weight management in Alzheimer's patients. ^{1 2 3 4 5}

Is THC-based medication safe for treating agitation in Alzheimer's patients?

Preliminary findings from a clinical trial suggest that dronabinol, a synthetic form of THC, is being studied for safety in treating agitation in Alzheimer's patients, but detailed safety data is not yet available. Another study is investigating the safety of nabilone, a synthetic cannabinoid, for similar purposes, indicating ongoing research into the safety of THC-based treatments for agitation in Alzheimer's. ^{1 2 3 5 6}

How is the drug IGC-AD1 different from other treatments for agitation in Alzheimer's?

IGC-AD1 is unique because it is a THC-based medication, which is being explored for its potential to relieve agitation in Alzheimer's patients by regulating neurotransmitters and improving circadian rhythms. Unlike other treatments, it leverages the anxiolytic (anxiety-reducing) and anti-inflammatory effects of cannabinoids, offering a novel approach in a field with no FDA-approved drugs for this condition. ^{1 2 3 4 5}

Research Team

Dr. Saadia Shahnawaz, MD

Principal Investigator

IGC Pharma, LLC

Eligibility Criteria

This trial is for adults with mild to severe Alzheimer's dementia experiencing significant agitation. Participants must have a caregiver able to assist and use electronic devices, be on stable behavioral medications for 3 months, and consent to genetic testing. Women should not be of childbearing potential.

Inclusion Criteria

Based on local practice, Participants that cannot consent may have Caregiver's consent provided the Caregiver has among others a) Power of Attorney, b) is a spouse, or c) a sibling or d) a child or e) a close relation. The practice of accepting consent must be consistent with established practice at the site and jurisdiction

The Caregiver must be known to the Participant and must be able to use electronic devices such as a cell phone, video conference over a laptop or cell phone, weighing scale, and be able to learn to take blood pressure, among others

Negative drug screen, except for benzodiazepines if Participant has been using them in stable doses for at least 3 months before screening

Exclusion Criteria

I do not have any serious illnesses that could affect the trial's safety assessment.

Has participated in an investigational drug or device study within 30 days prior to study start

I have a history of seizures, schizophrenia, or bipolar disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the oral medication IGC-AD1, a THC-based formulation, administered twice a day for 42 days

6 weeks

Daily calls on days 2, 3, and 4, then every third day

Taper

A two-day taper period at the end of the treatment phase

2 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IGC-AD1 (Cannabinoid)

Trial Overview The study tests IGC-AD1, a natural THC-based oral medication given in micro doses twice daily against a placebo, to manage symptoms of agitation in Alzheimer's patients.

Participant Groups

Group I: Active Comparator: IGC-AD1Active Active Control 1 Intervention

IGC-AD1-Active, oral solution with two APIs (THC and melatonin).

Group II: Placebo Comparator: IGC-AD1 Placebo Placebo Group 1 Intervention

IGC-AD1-Placebo, oral solution similar to Active in color, taste, and texture, with excipients but without APIs.

Who Is Running the Clinical Trial?

IGC Pharma, LLC

Lead Sponsor

Trials

2

Recruited

180+

IGC Pharma LLC

Lead Sponsor

Trials

2

Recruited

180+

Findings from Research

This ongoing clinical trial is investigating the safety and efficacy of dronabinol, a synthetic form of THC, as a treatment for agitation in Alzheimer's dementia, involving 80 participants over three weeks.

Preliminary data from 44 participants indicate a sample with significant cognitive impairment and agitation, suggesting that dronabinol could potentially address a critical gap in treatment options for Agit-AD, as there are currently no FDA-approved medications for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD). Cohen, LM., Ash, E., Outen, JD., et al.[2022]

A clinical trial is underway to evaluate nabilone, a synthetic cannabinoid, for treating agitation in patients with moderate-to-severe Alzheimer's disease, comparing its effects to a placebo over 6 weeks.

The study aims to assess not only the efficacy in reducing agitation but also the safety and potential benefits on pain, weight, and overall quality of life, which could help reduce caregiver stress and healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe Alzheimer's disease: Study protocol for a cross-over randomized controlled trial. Ruthirakuhan, MT., Herrmann, N., Gallagher, D., et al.[2022]

In a study involving 10 dementia patients, THC was found to be rapidly absorbed with dose-linear pharmacokinetics, showing significant interindividual variability in how patients responded to the drug.

Only a few adverse events were related to THC, indicating that it may be safe for use in dementia patients, although further research is needed to explore the effects and efficacy of higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. Ahmed, AI., van den Elsen, GA., Colbers, A., et al.[2022]

This meta-analysis of 6 studies involving 251 participants found that cannabinoids did not significantly reduce agitation in Alzheimer's patients, although there was a trend suggesting synthetic cannabinoids might be more effective than tetrahydrocannabinol.

Cannabinoid treatment was associated with increased sedation compared to placebo, indicating a need for careful monitoring of safety, but there were no significant differences in adverse events or dropouts due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids for Agitation and Aggression in Alzheimer's Disease: A Meta-Analysis. Ruthirakuhan, M., Lanctôt, KL., Vieira, D., et al.[2019]

Agitation in Alzheimer's disease is linked to brain volume loss in key areas and neurotransmitter degeneration, leading to a significant impact on patients' quality of life and increased caregiver burden.

Cannabinoids, such as CBD and THC, show promise as potential treatments for agitation in Alzheimer's due to their ability to regulate neurotransmitters, improve circadian rhythms, and enhance cerebral circulation, offering a safer alternative to current pharmacological options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids for Agitation in Alzheimer's Disease. Outen, JD., Burhanullah, MH., Vandrey, R., et al.[2022]

In a study of 30 Alzheimer's disease patients aged 65-90, the administration of a THC:CBD cannabis extract for 12 weeks significantly reduced symptoms such as agitation, irritability, and sleep disturbances, improving caregiver distress.

The study also found that 45% of patients showed a significant decrease in cognitive impairment, indicating potential efficacy of cannabis extracts in managing severe symptoms of Alzheimer's disease, despite limitations like the small sample size and lack of a control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss. Palmieri, B., Vadalà, M.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD). [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe Alzheimer's disease: Study protocol for a cross-over randomized controlled trial. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9-tetrahydrocannabinol in older persons with dementia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids for Agitation and Aggression in Alzheimer's Disease: A Meta-Analysis. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Cannabinoids for Agitation in Alzheimer's Disease. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss. [2023]