Clinical Trial on Agitation in Alzheimer's Dementia (CALMA)

May 18, 2026 updated by: IGC Pharma, LLC

A Phase 2, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Trial of the Safety and Efficacy of IGC-AD1 on Agitation in Participants With Dementia Due to Alzheimer's Disease

The purpose of this study is to assess the efficacy of the oral medication IGC-AD1, a THC-based (Delta-9-Tetrahydrocannabinol) formulation administered twice a day on Agitation in patients with mild to severe dementia from Alzheimer's.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CALMA is a multi-center, double-blind, randomized, placebo-controlled clinical trial. The study targets participants aged 60 and older with mild to severe Alzheimer's dementia who have exhibited clinically significant agitation for at least two weeks prior to enrollment. Agitation caused by other conditions or transient symptoms must be ruled out. Eligibility is determined by a baseline Neuropsychiatric Inventory (NPI-12), Agitation subscale score of ≥4 and the International Psychogeriatric Association (IPA) criteria for agitation.

The investigational medication is an oral solution containing two active ingredients: delta-9 tetrahydrocannabinol (THC) and melatonin. The treatment is administered for 42 days, followed by a two-day taper period at the end of the study.

Safety oversight includes daily calls on days 2, 3, and 4, transitioning to calls every third day thereafter. These calls will review study partners logbook entries, changes in concomitant medications, and adverse events.

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) scores from baseline to the End of treatment (EOT). The secondary objective is to assess efficacy by examining CMAI score changes from baseline to week two. Additionally, exploratory objectives are outlined in separate documentation.

Blood samples will be collected during the trial for sparse pharmacokinetic (PK) analysis, blood-based CNS biomarker, and genotyping.

Study Type

Interventional

Enrollment (Estimated)

164

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 1J8
        • Recruiting
        • Island Health Authorities
    • Ontario
      • Hamilton, Ontario, Canada, L8M 1W9
        • Recruiting
        • Hamilton Health Sciences , Mcmaster University
        • Contact:
      • Toronto, Ontario, Canada, ON M6A 2E1
        • Recruiting
        • Baycrest Academy for Research and Education , University of Toronto
    • Quebec
      • Montreal, Quebec, Canada, H4H 1R3
        • Recruiting
        • Douglas Hospital Research Center, McGill university
  • Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia
        • Active, not recruiting
        • Grupo de Neurociencias de Antioquia, Universidad de Antioquia
  • Puerto Rico
      • Bayamón, Puerto Rico, 00961
        • Recruiting
        • SCB Research Center Corp
      • Rio Piedras, Puerto Rico, 00935
        • Recruiting
        • The Alliance, Medical Sciences Campus University of Puerto Rico
    • Bayamón
      • Bayamón, Bayamón, Puerto Rico, 00961
        • Completed
        • Instituto Sanacoop
  • United States
    • Florida
      • Maitland, Florida, United States, 32751
        • Active, not recruiting
        • ClinCloud, LLC
      • Melbourne, Florida, United States, 32940
      • Miami, Florida, United States, 33125
        • Recruiting
        • Central Miami Medical Institute
      • Miami, Florida, United States, 33137
      • Miami, Florida, United States, 33133
        • Recruiting
        • Visionary Investigators Network
      • Port Charlotte, Florida, United States, 33952
      • St. Petersburg, Florida, United States, 33705
        • Recruiting
        • BayCare Health System Inc.
      • Tampa, Florida, United States, 33613
        • Recruiting
        • University of South Florida Department of Psychiatry and Behavioral Neurosciences
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • Recruiting
        • Tandem Clinical Research GI, LLC
    • Maryland
      • Baltimore, Maryland, United States, 21237
      • Clinton, Maryland, United States, 20735
        • Recruiting
        • MedStar Southern Maryland Hospital Center
      • Olney, Maryland, United States, 20832
    • Missouri
      • St Louis, Missouri, United States, 63128
        • Recruiting
        • Tekton Research LLC
    • New York
      • Amherst, New York, United States, 02459
        • Recruiting
        • Dent Neurologic Institute
      • Brooklyn, New York, United States, 11229
        • Recruiting
        • Integrative Clinical Trials, LLC
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
      • Syracuse, New York, United States, 13210
        • Recruiting
        • Ichor Research
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Recruiting
        • Lynn Health Science Institute (LHSI)
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Recruiting
        • Butler Hospital, Brown University
        • Contact:
    • Texas
      • Austin, Texas, United States, 78757
      • Dallas, Texas, United States, 75231
        • Recruiting
        • Kerwin Medical Center
      • Dallas, Texas, United States, 75231
        • Recruiting
        • Baylor Scott and White Research Institute
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Recruiting
        • Dominion Medical Associates, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

To be eligible to participate in this study, the participant must meet all the following criteria:

Inclusion Criteria

  1. Participant and/or Caregiver must provide a signed and dated ICF prior to any study procedures.
  2. Must have a Caregiver who is able and willing to comply with all required study procedures.
  3. 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.
  4. 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.
  5. Participants must consent to CYP450 and apolipoprotein E (ApoE) genotyping, and pharmacokinetics.
  6. Diagnosis of AD by NIA-AA criteria

  7. Clinically significant Agitation assessed by:

    1. NPI (Agitation) ≥ 4
    2. The presence of clinically significant, persistent Agitation based on the IPA definition (Appendix C) rather than those with recent onset and occasional symptoms, and
    3. Agitation not attributable to another psychiatric disorder, suboptimal care conditions, other underlining medical condition, or the physiological effects of a substance.
  8. Negative drug screen, except for benzodiazepines if Participant has been using them in stable doses for at least 3 months before screening.
  9. All medications used for behavioral symptoms should be consistent for at least 6 weeks before screening, with allowance for dose changes up to 25%.
  10. Women must be of no childbearing potential (postmenopausal, defined as cessation of menses for at least 12 months, without an alternative medical cause for amenorrhea) or surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation)).

An individual who meets any of the following criteria will be excluded from participation in this study:

Exclusion Criteria

  1. Prior adverse reaction to cannabinoids or to any component of Study Drug (IGC-AD1 and placebo).
  2. Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease, which might confound assessment of safety outcomes.
  3. History of seizures, schizophrenia, or bipolar disorder.
  4. Has participated in an investigational drug or device study within 30 days prior to study start.
  5. Urine drug screen positive for drug use, except for benzodiazepines if Participant was using them previously and their dose had remained stable for at least six weeks before screening.
  6. History of Alcohol and Drug use disorder, within one year prior to enrollment.
  7. Hypertension: Participants with a history of uncontrolled hypertension as determined by the PI and Participants with a hypertensive crisis in the six months prior to enrollment.
  8. Falls: Participants with a history of recurrent falls defined as more than two falls in the six-month period prior to enrollment and a history of falls resulting in injuries or associated with a new acute illness, loss of consciousness, fever, or abnormal blood pressure (Fuller et al., 2000).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Comparator: IGC-AD1Active
IGC-AD1-Active, oral solution with two APIs (THC and melatonin).
Drug: IGC-AD1-Active
A non-sterile solution for oral administration.
Other Names:
  • Active
Placebo Comparator: Placebo Comparator: IGC-AD1 Placebo
IGC-AD1-Placebo, oral solution similar to Active in color, taste, and texture, with excipients but without APIs.
Drug: IGC-AD1-Placebo
A non-sterile solution for oral administration similar in color and texture to the Active.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Agitation
Time Frame: Baseline to week six
Change in mean Cohen Mansfield Agitation Inventory (CMAI) score
Baseline to week six

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Agitation
Time Frame: Baseline to week two
Change in mean Cohen Mansfield Agitation Inventory (CMAI) score
Baseline to week two

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Agitation at week four
Time Frame: Baseline to week four
Change in mean Cohen Mansfield Agitation Inventory (CMAI) score
Baseline to week four
Participant overall wellbeing
Time Frame: Baseline to weeks two and six
Change in the Clinical Global Impression Scale (CGI)
Baseline to weeks two and six
Participant executive functions
Time Frame: Baseline to week six
Change in Mini-Mental State Examination (MMSE2) score
Baseline to week six
Depression
Time Frame: Baseline to weeks two, four, and six
Change in mean Cornell Scale for Depression in Dementia (CSDD) score
Baseline to weeks two, four, and six
Neuropsychiatric symptoms
Time Frame: Baseline to weeks two, four, and six
Change in mean Neuropsychiatric Inventory (NPI-12) score
Baseline to weeks two, four, and six
Participant quality of life
Time Frame: Baseline to weeks two, four and six
Change in mean Quality of Life in Alzheimer's Disease (QOL-AD) score
Baseline to weeks two, four and six
Caregiver burden
Time Frame: Baseline to weeks two and six
Change in mean Zarit Burden Interview (ZBI) score
Baseline to weeks two and six
Psychotropic drugs
Time Frame: Baseline to six weeks
Change in type and dosage of psychotropic drugs
Baseline to six weeks
CYP2C9 polymorphisms on agitation
Time Frame: Baseline to weeks two, four and six
Change in mean Cohen Mansfield Agitation Inventory (CMAI) score for each type of metabolizer group (*1/*1, *1/*3, etc.)
Baseline to weeks two, four and six

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IGC Pharma, LLC

Investigators

  • Study Director: Dr. Saadia Shahnawaz, MD, IGC Pharma, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2022

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

September 14, 2022

First Submitted That Met QC Criteria

September 14, 2022

First Posted (Actual)

September 16, 2022

Study Record Updates

Last Update Posted (Actual)

May 20, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IGC-AD1-P2 BIDAG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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