Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease

NCT04436081 | Unknown Phase 2 FDA Drug

• 1 other identifier: RI-03368
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blinded, placebo-controlled, crossover trial that aims to 1) determine the efficacy of THC-free cannabidiol (CBD oil) in reducing the severity of agitation among participants and 2) determine whether THC-free CBD oil can reduce the burden on caregivers and increase the participants' quality of life.

Conditions

Alzheimer Disease; Dementia; Major Neurocognitive Disorder With Aggressive Behavior

Keywords

Agitation; Aggression; Neuropsychiatric symptoms; CBD Oil; Cannabinoids; Caregiver burden; Sleep quality; Behavioral and Psychological Symptoms of Dementia; Neurocognitive disorders; Psychomotor agitation; Cannabidiols

Outcome Measures

Primary Outcomes (4)

• Change in agitation and aggression.

  Change in agitation and aggression will be measured by the Cohen-Mansfield Agitation Inventory (CMAI), a validated 29-item questionnaire to assess agitation. Each item is rated on a 7-point scale ranging from 1 "Never" to 7 "Several times per hour". Higher scores indicate greater agitation.

  Every two weeks for 15 weeks during study enrollment.

• Change in caregiver burden.

  Change in caregiver burden will be measured by the Zarit Burden Interview (ZBI), a validated 22-item questionnaire to assess caregiver burden. Each item is rated on a 5-point Likert scale that ranges from 0 "Never" to 4 "Nearly always," with the sum of scores ranging between 0-88. Higher scores indicate greater burden.

  Three times during the 15 weeks of study enrollment.

• Change in the participant's quality of life.

  Change in the participant's quality of life will be measured by the Quality-of-life assessment in dementia (DEMQOL-proxy), a validated 32-item questionnaire to assess the health related quality of life of people with dementia. Each item is rated on a 4-point scale ranging from 1 "A lot" to 4 "Not at all". Higher scores indicate a healthier quality of life.

  Three times during the 15 weeks of study enrollment.

• Change in caregiver's quality of life.

  Change in the caregiver's quality of life will be measured by the Measurement of quality of life in family carers of people with dementia (C-DEMQOL), a validated 30-item questionnaire to assess the quality of life for carers of someone with dementia. Each item is rated on a 5-point scale ranging from 1 "Completely" to 5 "Not at all." Higher scores indicate a healthier quality of life.

  Three times during the 15 weeks of study enrollment.

Secondary Outcomes (3)

• Assessment of change in neuropsychiatric symptoms.

  Three times during the 15 weeks of study enrollment.

• Assessment of change in cognitive skills.

  Three times during the 15 weeks of study enrollment.

• The effect of CBD oil on sleep quantity measured by Fitbit

  Measured on a daily basis during the 15 weeks of study enrollment.

Study Arms (2)

Hemp-based CBD oil Gelcaps

ACTIVE COMPARATOR

The intervention consists of 6 weeks oral administration of CBD oil Gelcaps, starting at a dosage of 15 mg twice per day with up titration to 45 mg twice per day. At any given dose, if participants develop side effects, the dosage will be reduced to the previous dose.

Drug: THC-free CBD Oil

Oral placebo Gelcaps

PLACEBO COMPARATOR

Participants in the control group will receive oral placebo Gelcaps that are identical in appearance to the CBD oil Gelcaps. Dosing will be identical to the intervention arm.

Drug: Placebo

Interventions

THC-free CBD Oil DRUG

Hemp-based CBD oil Gelcaps

Hemp-based CBD oil Gelcaps

Placebo DRUG

Placebo Gelcaps

Oral placebo Gelcaps

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males/females over 50 years old.
• Have a diagnosis of dementia due to AD or mixed AD with another type of dementia.
• A Mini-Mental State Exam score (MMSE) between 4 and 28 inclusive.
• Presence of agitation with a Neuropsychiatric Inventory (NPI)-agitation/aggression subscore \> 3.
• Participants and their informal caregivers must be fluent in English (includes reading, writing, and speech) and able to give informed consent.
• For patients treated with cognitive-enhancing medications (cholinesterase inhibitors (ChEI) and/or memantine), the dosage must be stable for at least 1 month (30 days). If the ChEI and/or memantine has been discontinued, patients may enroll after 15 days.
• Eligible caregivers must either live with the participant or have a minimum of 4 hours of daily contact with them.

You may not qualify if:

• Diagnosis of non-AD or non-mixed dementias.
• Very mild dementia or advanced dementia (MMSE: greater than 28 or less than 4).
• NPI-agitation-aggression score \< 3.
• Having a serious or unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease which might confound assessment of safety outcomes as determined by the study physician.
• Presence or history of other serious psychiatric disorders or neurological conditions (e.g. psychotic disorders, bipolar disorder or schizophrenia).
• Current abuse of/dependence on marijuana, current drug abuse, current alcohol abuse.
• Having seizure disorders.
• Pregnant or breastfeeding
• Indication of baseline delirium as determined by the Confusion Assessment Method (CAM).
• Current use of lithium.
• Inability to swallow CBD oil softgels.
• Changes in dosage of anti-depressives within 4 weeks before randomization and during the study.
• Changes in dosage of antipsychotics or benzodiazepines within 1 week prior to randomization and during the study.
• Contraindications to CBD oil (history of hypersensitivity to any cannabinoid).
• Frequent falling due to orthostatic hypotension.

Sponsors & Collaborators

• Eastern Virginia Medical School: lead
• Old Dominion University: collaborator
• Ananda Hemp, Inc.: collaborator

Study Sites (1)

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

RECRUITING

Related Publications (13)

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  PMID: 22586419 BACKGROUND

• van der Linde RM, Dening T, Stephan BC, Prina AM, Evans E, Brayne C. Longitudinal course of behavioural and psychological symptoms of dementia: systematic review. Br J Psychiatry. 2016 Nov;209(5):366-377. doi: 10.1192/bjp.bp.114.148403. Epub 2016 Aug 4.

  PMID: 27491532 BACKGROUND

• Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015 Mar 2;350:h369. doi: 10.1136/bmj.h369.

  PMID: 25731881 BACKGROUND

• Okura T, Langa KM. Caregiver burden and neuropsychiatric symptoms in older adults with cognitive impairment: the Aging, Demographics, and Memory Study (ADAMS). Alzheimer Dis Assoc Disord. 2011 Apr-Jun;25(2):116-21. doi: 10.1097/WAD.0b013e318203f208.

  PMID: 21192239 BACKGROUND

• Yaffe K, Fox P, Newcomer R, Sands L, Lindquist K, Dane K, Covinsky KE. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA. 2002 Apr 24;287(16):2090-7. doi: 10.1001/jama.287.16.2090.

  PMID: 11966383 BACKGROUND

• Khan SS, Ye B, Taati B, Mihailidis A. Detecting agitation and aggression in people with dementia using sensors-A systematic review. Alzheimers Dement. 2018 Jun;14(6):824-832. doi: 10.1016/j.jalz.2018.02.004. Epub 2018 Mar 20.

  PMID: 29571749 BACKGROUND

• Cummings J, Lee G, Ritter A, Zhong K. Alzheimer's disease drug development pipeline: 2018. Alzheimers Dement (N Y). 2018 May 3;4:195-214. doi: 10.1016/j.trci.2018.03.009. eCollection 2018.

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• Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994 Dec;44(12):2308-14. doi: 10.1212/wnl.44.12.2308.

  PMID: 7991117 BACKGROUND

• Cohen-Mansfield J, Marx MS, Rosenthal AS. A description of agitation in a nursing home. J Gerontol. 1989 May;44(3):M77-84. doi: 10.1093/geronj/44.3.m77.

  PMID: 2715584 BACKGROUND

• Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist. 1980 Dec;20(6):649-55. doi: 10.1093/geront/20.6.649. No abstract available.

  PMID: 7203086 BACKGROUND

• Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.

  PMID: 1202204 BACKGROUND

• Smith SC, Lamping DL, Banerjee S, Harwood RH, Foley B, Smith P, Cook JC, Murray J, Prince M, Levin E, Mann A, Knapp M. Development of a new measure of health-related quality of life for people with dementia: DEMQOL. Psychol Med. 2007 May;37(5):737-46. doi: 10.1017/S0033291706009469. Epub 2006 Dec 19.

  PMID: 17176501 BACKGROUND

• Smith SC, Lamping DL, Banerjee S, Harwood R, Foley B, Smith P, Cook JC, Murray J, Prince M, Levin E, Mann A, Knapp M. Measurement of health-related quality of life for people with dementia: development of a new instrument (DEMQOL) and an evaluation of current methodology. Health Technol Assess. 2005 Mar;9(10):1-93, iii-iv. doi: 10.3310/hta9100.

  PMID: 15774233 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Psychomotor Agitation; Aggression; Caregiver Burden; Sleep Initiation and Maintenance Disorders; Behavior; Neurocognitive Disorders

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Mental Disorders; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Social Behavior; Stress, Psychological; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders

Study Officials

• Hamid Okhravi, MD

  Eastern Virginia Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Elkins, MS

CONTACT

757.446.5675; ELKINSDE@evms.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Geriatrics and Director of Memory Clinic

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: June 17, 2020
• Study Start: February 26, 2021
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)