Clinical trial NCT05543681: Clinical Trial on Agitation in Alzheimer's Dementia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Agitation,Psychomotor
Care Giving Burden
NPS
Aggression
Keywords: Cannabis
Tetrahydrocannabinol
THC
Melatonin
Alzheimer's
Marijuana
Hemp
Agitation
Dementia
Depression
Anxiety
NPI
CMAI
Dronabinol
Lead sponsor: IGC Pharma, LLC
Sponsor class: INDUSTRY
First posted: 2022-09-16
Enrollment: 164
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-site, Randomized, double-blind, placebo-controlled parallel-group trial in adults with mild to severe dementia from Alzheimer's and symptomatological Agitation.
Primary purpose: TREATMENT

Brief summary: 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.

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.

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 3 months 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): THC, melatonin, honey, curcumin, ethyl alcohol, vitamin-E TPGS, ascorbic acid, water, tween-80, and rutin.
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 3 months 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:
measure: Agitation
timeFrame: Baseline to week six
Secondary outcomes:
measure: Acute Agitation
timeFrame: Baseline to week two
Other outcomes:
measure: Agitation at week four
timeFrame: Baseline to week four
measure: Participant overall wellbeing
timeFrame: Baseline to weeks two and six
measure: Participant executive functions
timeFrame: Baseline to week six
measure: Depression
timeFrame: Baseline to weeks two, four, and six
measure: Neuropsychiatric symptoms
timeFrame: Baseline to weeks two, four, and six
measure: Participant quality of life
timeFrame: Baseline to weeks two, four and six
measure: Caregiver burden
timeFrame: Baseline to weeks two and six
measure: Psychotropic drugs
timeFrame: Baseline to six weeks
measure: CYP2C9 polymorphisms on agitation
timeFrame: Baseline to weeks two, four and six
Locations:
city: Maitland
country: United States
facility: ClinCloud, LLC
state: Florida
city: Melbourne
country: United States
facility: ClinCloud, LLC
state: Florida
city: Miami
country: United States
facility: Global Medical Institutes Florida, LLC
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: BayCare Health System Inc.
state: Florida
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center Neurology
state: Maryland
city: Clinton
country: United States
facility: Medstar Georgetown University Hospital Neurology
state: Maryland
city: Olney
country: United States
facility: Medstar Montgomery Medical Center
state: Maryland
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute (LHSI)
state: Oklahoma
city: Yukon
country: United States
facility: Tekton Research LLC
state: Oklahoma
city: Providence
country: United States
facility: Butler Hospital, Brown University
state: Rhode Island
city: Austin
country: United States
facility: Senior Adults Specialty Research
state: Texas
city: Victoria
country: Canada
facility: Island Health Authorities
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences , Mcmaster University
state: Ontario
city: Toronto
country: Canada
facility: Baycrest Academy, University of Toronto
state: Ontario
city: Montréal
country: Canada
facility: Douglas Hospital Research Center, McGill university
state: Quebec
city: Medellín
country: Colombia
facility: Grupo de Neurociencias de Antioquia, Universidad de Antioquia
state: Antioquia
city: Bayamón
country: Puerto Rico
facility: Instituto Sanacoop
city: Bayamón
country: Puerto Rico
facility: SCB Research Center
city: Rio Piedras
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: IGC Pharma, LLC
name: Dr. Saadia Shahnawaz, MD
role: STUDY_DIRECTOR
References: