INTERVENTIONALRECRUITINGNCT05543681

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.

Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2026-05-20

What this record can show

Protocol only - no registry results posted

This locally preserved record separates the registered protocol from source-reported registry results. Neither is a treatment recommendation.

Registry facts

Study at a glance

Phase: PHASE2
Enrollment: 164 (ESTIMATED)
Start date: 2022-10-11
Sponsor: IGC Pharma, LLC
Design: RANDOMIZED · PARALLEL · TREATMENT
Locations: 31
Results record: Not present in registry snapshot

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.

Linked local records

Related local records

Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.

Conditions

Alzheimer Disease

Cannabinoids and active compounds

No governed compound link was found.

Medicines

No exact medicine-name link was found.

Interventions

What was registered

DRUG

IGC-AD1-Active

A non-sterile solution for oral administration.

Active

DRUG

IGC-AD1-Placebo

A non-sterile solution for oral administration similar in color and texture to the Active.

Placebo

Eligibility

Population and criteria

Sex: ALL
Minimum age: 60 Years
Maximum age: Not reported
Healthy volunteers: Not accepted

Eligibility criteria

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).

primary outcomes

primary measures

Agitation

Time frame: Baseline to week six

Change in mean Cohen Mansfield Agitation Inventory (CMAI) score

secondary outcomes

secondary measures

Acute Agitation

Time frame: Baseline to week two

Change in mean Cohen Mansfield Agitation Inventory (CMAI) score

other outcomes

other measures

Agitation at week four

Time frame: Baseline to week four

Change in mean Cohen Mansfield Agitation Inventory (CMAI) score

Participant overall wellbeing

Time frame: Baseline to weeks two and six

Change in the Clinical Global Impression Scale (CGI)

Participant executive functions

Time frame: Baseline to week six

Change in Mini-Mental State Examination (MMSE2) score

Depression

Time frame: Baseline to weeks two, four, and six

Change in mean Cornell Scale for Depression in Dementia (CSDD) score

Neuropsychiatric symptoms

Time frame: Baseline to weeks two, four, and six

Change in mean Neuropsychiatric Inventory (NPI-12) score

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

Caregiver burden

Time frame: Baseline to weeks two and six

Change in mean Zarit Burden Interview (ZBI) score

Psychotropic drugs

Time frame: Baseline to six weeks

Change in type and dosage of psychotropic drugs

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.)

Publications

Locally readable linked articles

No exact PMID-linked public article is currently readable locally.

Snapshot provenance

Snapshot: 50927c3d-921a-4851-bf94-80e94c8ad66e
Retrieved: 11/09/2026, 14:54:04
SHA-256: 5af3f4bd9a3fb636691441164f4cdcae93d50d8a56fbb0beb36bda55cb6dd06b