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

Primary Purpose

Alzheimer Disease, Dementia, Major Neurocognitive Disorder With Aggressive Behavior

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
THC-free CBD Oil
Placebo
Sponsored by
Eastern Virginia Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Agitation, Aggression, Neuropsychiatric symptoms, CBD Oil, Cannabinoids, Caregiver burden, Sleep quality, Behavioral and Psychological Symptoms of Dementia, Neurocognitive disorders, Psychomotor agitation, Cannabidiols

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Use of tricyclic antidepressants (TCA), fluoxetine, and/or carbamazepine. -Patients who reside in nursing homes.

Sites / Locations

  • Eastern Virginia Medical SchoolRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hemp-based CBD oil Gelcaps

Oral placebo Gelcaps

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Assessment of change in neuropsychiatric symptoms.
Assessment of change in neuropsychiatric symptoms for the participant will be measured by the Neuropsychiatric Inventory (NPI), a validated questionnaire that assesses dementia-related behavioral symptoms. The NPI examines 12 sub-domains of behavioral functioning. Each sub-domain is rated on the frequency of the symptoms using a 4-point scale with 1 "Occasionally" and 4 "Very frequently", the severity of the symptoms using a 3-point scale with 1 "Mild" and 3 "Marked", and the distress the symptom causes them on a 5-point scale with 1 "Not at all" and 5 "Very severely or extremely".
Assessment of change in cognitive skills.
Assessment of change in cognitive skills for the participant will be measured by the Mini Mental State Exam (MMSE), a validated 30-item questionnaire used to measure cognitive impairment among the elderly. A 30-item, clinician-administered assessment of orientation, attention, calculation, learning and memory, language, and visuospatial skills. Each correct response is summed to produce a total score out of 30 possible points.
The effect of CBD oil on sleep quantity measured by Fitbit
The effect of CBD oil on sleep quality will be measured for the participant and caregiver using the actigraphy function of fit bit. These measures include the amount of total sleep, amount of rapid eye movement (REM) sleep and the amount of deep and light sleep.

Full Information

First Posted
June 12, 2020
Last Updated
February 15, 2023
Sponsor
Eastern Virginia Medical School
Collaborators
Old Dominion University, Ananda Hemp, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04436081
Brief Title
Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease
Official Title
Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 26, 2021 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Eastern Virginia Medical School
Collaborators
Old Dominion University, Ananda Hemp, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Individuals with Alzheimer's and other forms of dementia often go through a period of significant behavioral and psychological symptoms of dementia (BPSD). It is estimated that up to 90% of persons with dementia (PWD) experience behavior problems at some point. BPSDs can be challenging for both unpaid family caregivers as well as paid caregivers. Family caregivers provide the bulk of care for PWD and number over 15 million. One of the most common types of BPSDs is agitation with a prevalence of up to 87%, based on a recent systematic review. Agitation can lead to impaired daily functioning, prolongation of hospitalization, reduced time to institutionalization, and is associated with higher mortality. Additionally, agitated behavior is associated with increased injury to both patients and caregivers. Based on the 2018 Alzheimer's disease drug development pipeline report almost 70% of clinical trials related to BPSD are dedicated to agitation behavior. Finding ways to address agitation is necessary to improve overall quality of life for PWD and their caregivers. Currently, there are no medications available specifically for the treatment of BPSDs. The use of benzodiazepines, antipsychotics and mood stabilizing agents are common, but the risks and side effects often outweigh any benefits. Several small studies have investigated the use of cannabinoids in the treatment of pathology and symptomology of Alzheimer's disease (AD), as well as treatment of the agitation component of BPSD. A handful of these studies showed that the symptoms of BPSD were decreased with the use of cannabinoids. However, due to small sample sizes, study design, and short trial duration of these studies, the efficacy of these agents on BPSD cannot be confirmed. In addition, cannabinoids have demonstrated anti-oxidant and anti-inflammatory effects, and both processes have been indicated as major contributors to the neurologic effects of AD. Some evidence exists that agitation is related to this neuroinflammatory process. This study will examine the effects of cannabinoids on the behavioral and psychological symptoms of individuals with a dementia diagnosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hemp-based CBD oil Gelcaps
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Oral placebo Gelcaps
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
THC-free CBD Oil
Intervention Description
Hemp-based CBD oil Gelcaps
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Gelcaps
Primary Outcome Measure Information:
Title
Change in agitation and aggression.
Description
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.
Time Frame
Every two weeks for 15 weeks during study enrollment.
Title
Change in caregiver burden.
Description
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.
Time Frame
Three times during the 15 weeks of study enrollment.
Title
Change in the participant's quality of life.
Description
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.
Time Frame
Three times during the 15 weeks of study enrollment.
Title
Change in caregiver's quality of life.
Description
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.
Time Frame
Three times during the 15 weeks of study enrollment.
Secondary Outcome Measure Information:
Title
Assessment of change in neuropsychiatric symptoms.
Description
Assessment of change in neuropsychiatric symptoms for the participant will be measured by the Neuropsychiatric Inventory (NPI), a validated questionnaire that assesses dementia-related behavioral symptoms. The NPI examines 12 sub-domains of behavioral functioning. Each sub-domain is rated on the frequency of the symptoms using a 4-point scale with 1 "Occasionally" and 4 "Very frequently", the severity of the symptoms using a 3-point scale with 1 "Mild" and 3 "Marked", and the distress the symptom causes them on a 5-point scale with 1 "Not at all" and 5 "Very severely or extremely".
Time Frame
Three times during the 15 weeks of study enrollment.
Title
Assessment of change in cognitive skills.
Description
Assessment of change in cognitive skills for the participant will be measured by the Mini Mental State Exam (MMSE), a validated 30-item questionnaire used to measure cognitive impairment among the elderly. A 30-item, clinician-administered assessment of orientation, attention, calculation, learning and memory, language, and visuospatial skills. Each correct response is summed to produce a total score out of 30 possible points.
Time Frame
Three times during the 15 weeks of study enrollment.
Title
The effect of CBD oil on sleep quantity measured by Fitbit
Description
The effect of CBD oil on sleep quality will be measured for the participant and caregiver using the actigraphy function of fit bit. These measures include the amount of total sleep, amount of rapid eye movement (REM) sleep and the amount of deep and light sleep.
Time Frame
Measured on a daily basis during the 15 weeks of study enrollment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. Use of tricyclic antidepressants (TCA), fluoxetine, and/or carbamazepine. -Patients who reside in nursing homes.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Elkins, MS
Phone
757.446.5675
Email
ELKINSDE@evms.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hamid Okhravi, MD
Organizational Affiliation
Eastern Virginia Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Eastern Virginia Medical School
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hamid Okhravi, MD
Phone
757-446-7040
Email
okhravHR@evms.edu
First Name & Middle Initial & Last Name & Degree
Hamid Okhravi, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22586419
Citation
Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. Behavioral and psychological symptoms of dementia. Front Neurol. 2012 May 7;3:73. doi: 10.3389/fneur.2012.00073. eCollection 2012.
Results Reference
background
PubMed Identifier
27491532
Citation
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.
Results Reference
background
PubMed Identifier
25731881
Citation
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.
Results Reference
background
PubMed Identifier
21192239
Citation
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.
Results Reference
background
PubMed Identifier
11966383
Citation
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.
Results Reference
background
PubMed Identifier
29571749
Citation
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.
Results Reference
background
PubMed Identifier
29955663
Citation
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.
Results Reference
background
PubMed Identifier
7991117
Citation
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.
Results Reference
background
PubMed Identifier
2715584
Citation
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.
Results Reference
background
PubMed Identifier
7203086
Citation
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.
Results Reference
background
PubMed Identifier
1202204
Citation
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.
Results Reference
background
PubMed Identifier
17176501
Citation
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.
Results Reference
background
PubMed Identifier
15774233
Citation
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.
Results Reference
background

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

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