THC-Based Medication for Agitation in Alzheimer's

(CALMA Trial)

Recruiting at 44 trial locations

Overseen By Margarita Venegas

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: IGC Pharma, LLC

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication called IGC-AD1, based on THC (the active ingredient in cannabis), to see if it can reduce agitation in people with Alzheimer's disease. The study aims to determine the medication's effectiveness and safety for patients with significant and persistent agitation. Participants will receive either the active medication or a placebo (a look-alike treatment with no active ingredients). Individuals diagnosed with Alzheimer's who frequently experience agitation may be a good fit for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to important advancements in Alzheimer's care.

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.

Is there any evidence suggesting that IGC-AD1 is likely to be safe for humans?

Research has shown that IGC-AD1, a medicine made from THC, is safe and well-tolerated in earlier studies. These studies tested various doses of IGC-AD1 and found that patients experienced no serious side effects. At the doses tested, patients did not encounter major health issues. The treatment combines THC with melatonin and aims to reduce restlessness in people with Alzheimer's disease. The available data reported no serious health problems, making it a promising option for those considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about IGC-AD1 for agitation in Alzheimer's patients because it combines THC and melatonin in a unique oral solution. Unlike typical treatments that rely on antipsychotics or antidepressants, which mainly target mood symptoms, IGC-AD1 uses THC to potentially reduce agitation by interacting directly with the brain's endocannabinoid system. The addition of melatonin may also help regulate sleep, addressing common disturbances in Alzheimer's. This dual-action approach could offer a more balanced and targeted method to manage agitation, potentially with fewer side effects.

What evidence suggests that IGC-AD1 might be an effective treatment for agitation in Alzheimer's?

Research has shown that IGC-AD1, a treatment made from THC, might help reduce agitation in people with Alzheimer's. In this trial, participants will receive either the active IGC-AD1 treatment or a placebo. Early results from past studies indicated that patients using IGC-AD1 experienced a greater decrease in agitation compared to those who took a placebo. Additionally, IGC-AD1 seems to help with sleep problems, which are common in Alzheimer's. The treatment may work by reducing a process that damages brain cells in Alzheimer's. These findings suggest that IGC-AD1 could effectively manage agitation symptoms in Alzheimer's patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Dr. Saadia Shahnawaz, MD

Principal Investigator

IGC Pharma, LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• IGC-AD1

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05543681

Clinical Trial on Agitation in Alzheimer's Dementia (CALMA) The primary objective of the study is to evaluate the efficacy of IGC-AD1 on agitation, measured by changes in the Cohen-Mansfield Agitation Inventory (CMAI) ...

2. investor.igcpharma.com investor.igcpharma.com/igc-pharmas-phase-2-clinical/

IGC Pharma's Phase 2 Clinical Trial Interim Data ... The results suggest that IGC-AD1 may decrease the frequency and/or severity of sleep disturbances and nighttime behaviors, addressing a critical yet ...

3. drug-dev.com drug-dev.com/igc-pharma-announces-positive-interim-results-for-igc-ad1-in-reducing-alzheimers-agitation/

IGC Pharma Announces Positive Interim Results for ... Based on interim data, patients taking IGC-AD1, on average, experienced a more significant reduction in agitation scores compared to those on placebo, and the ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/igc-trial-alzheimers/

IGC adds new site for trial of Alzheimer's agitation therapy IGC Pharma has added HHS in Canada as a new clinical site for its Phase II CALMA trial of IGC-AD1 to treat agitation in Alzheimer's disease.

5. investor.igcpharma.com investor.igcpharma.com/igc-pharma-announces-additional-data/

IGC Pharma Announces Additional Data Supporting ... The data shows that IGC-AD1 effectively reduced hyperphosphorylation of tau protein, a process strongly associated with the formation of neurofibrillary tangles ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05543681

Clinical Trial on Agitation in Alzheimer's Dementia (CALMA) The primary objective of the study is to evaluate the efficacy of IGC-AD1 on agitation, measured by changes in the Cohen-Mansfield Agitation Inventory (CMAI) ...

7. igcpharma.com igcpharma.com/igc-ad1/

IGC-AD1 ... Alzheimer's disease to evaluate the safety and tolerability of IGC-AD1. Results: IGC-AD1 was found to be safe and tolerable at three different dosage levels.

8. withpower.com withpower.com/trial/phase-2-dementia-8-2022-c6b8a

THC-Based Medication for Agitation in Alzheimer's 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 ...

9. investor.igcpharma.com investor.igcpharma.com/igc-ad1-interim-phase-2/

IGC-AD1's Interim Phase 2 Data Show a Reduction in ... IGC-AD1 is currently undergoing a Phase 2 clinical trial for agitation in dementia associated with Alzheimer's (clinicaltrials.gov, CT05543681).

10. ctv.veeva.com ctv.veeva.com/study/igc-ad1-trial-on-agitation-in-dementia-due-to-alzheimers

Clinical Trial on Agitation in Alzheimer's Dementia (CALMA) The primary objective of the study is to evaluate the efficacy of IGC-AD1 on agitation, measured by changes in the Cohen-Mansfield Agitation ...