Life's End Benefits of cannaBidiol and tetrahYdrocannabinol (LiBBY)

Life's End Benefits of cannaBidiol and tetrahYdrocannabinol (LiBBY)

This is a multicenter randomized double-blind placebo-controlled Phase 2 study of an oral combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) compared to placebo over 12 weeks. This study is designed to test the hypothesis that treatment with an oral combination of THC/CBD will reduce agitation hospice care-eligible patients with agitation and dementia as measured by the Cohen Mansfield Agitation Inventory (CMAI) when compared to placebo at 2 weeks.

This study will enroll approximately 120 participants of any gender at least 40 years of age who are hospice care-eligible with agitation and dementia (HAD). Participants will be randomized (50:50) to either active study drug (T2:C100) or placebo.

The double-blind period of this study is 12 weeks. A 12 week optional open-label extension will be offered to participants who complete the double-blind period.

Study Overview

• Status: Active, not recruiting
• Conditions: Dementia; Agitation
• Intervention / Treatment: Drug: T2:C100; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University
    • Washington D.C., District of Columbia, United States, 20059
      • Howard University
  • Florida
    • Miami, Florida, United States, 33145
      • Melgar-Caro Medcenter and Community Research (MCMCR)
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • University of Kentucky
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Case Western Reserve University
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center Center for Cognitive Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent from participant or legally authorized representative.
2. Person of any sex/gender 40 years of age or older.
3. Ability to take or be administered liquid medication.
4. Meets DSM-V criteria for Major Neurocognitive Disorder.
5. Current clinically significant agitation as demonstrated by an NPI-agitation subscale of 4 or above at Screening.

6. Meets at least one of the following requirements:

   1. Currently enrolled in out-patient or in-patient hospice care.
   2. Stage 6d on the Functional Assessment Staging Test (FAST).
   3. Score of 12 or more according to the Advanced Dementia Prognostic Tool (ADEPT) as implemented by the Mitchell Index.
7. Willing to agree not to use cannabinoids in any form (e.g., topically applied, ingested, inhaled, or other form of administration), other than the trial medication, during the first 12 weeks of the study.
8. Has a third-party clinician (e.g., hospice, palliative care, PCP) who is responsible for medical management of the participant outside the study.
9. In the opinion of the investigator, resides in an environment suitable to conduct a clinical trial (i.e., study intervention can be administered and concomitant medication use can be accurately documented).

10. In the opinion of the site PI, has a study partner (may be paid or unpaid caregiver) able and willing to provide accurate information about the participant, oversee the administration of study drug, and participate in study visits and informant-based assessments (usually requires at least 5 hours of contact per week).

    NOTE: Other knowledgeable informants/informed caregivers may contribute to informant-based scales; however, the site should identify an informant who will be able to serve as the primary source of information.

11. As assessed by investigator, participant is likely to be able to comply with the protocol for a minimum of 2 weeks.

Exclusion Criteria:

1. Use of cannabinoids or other forms of marijuana in the 3 weeks prior to Baseline, as based on self-report.
2. Suspected or known allergic reactions, adverse reactions, or hypersensitivity to cannabinoids and/or components (e.g., (<specify oil to be used in final formulation, e.g.: coconut oil; sesame oil>) of the study drug (T2:C100 or placebo).
3. Treatment with another investigational drug or other investigational intervention within the previous 30 days or five half-lives of the investigational product, whichever is longer.
4. Any condition, which in the opinion of the site PI, Data and Coordinating Center, regulatory sponsor, or Project Lead/Protocol PI, makes the participant unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo in a digestible oil. The placebo contains only three non-reactive ingredients: medium chain triglyceride (MCT) oil and two flavoring agents (lemon and peppermint). During the double-blind treatment period, participants will receive 1mL placebo twice daily for Baseline - Day 7 (approximately 1 week), and then will increase to 2mL placebo twice for the remainder of the double-blind treatment period (Day 7 - Week 12 (approximately 11 weeks)).
Experimental: T2:C100	Drug: T2:C100; The active study intervention, T2:C100, is an oral combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) in a digestible oil. T2:C100 is a full spectrum oral solution with five non-reactive ingredients: delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), a pharmaceutical grade medium chain triglyceride (MCT) oil, and two flavoring agents (lemon and peppermint). During the double-blind treatment period, participants will receive 1mL study drug (T2:C100) twice daily for Baseline - Day 7 (approximately 1 week), and then will increase to 2mL study drug twice for the remainder of the double-blind treatment period (Day 7 - Week 12 (approximately 11 weeks)). Participants who enter the Open Label Extension will receive 1mL study drug (T2:C100) twice daily for Week 12 - Week 13 (approximately 1 week), and will then increase to 2mL study drug twice daily for the remainder of the Open Label Extension (Week 13 - Week 26 (approximately 23 weeks)).; Other Names: TRC/CBD oral combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in agitation as measured by the Cohen-Mansfield Agitation Inventory (CMAI) at 2 weeks	The Cohen-Mansfield Agitation Inventory (CMAI) assesses the average frequency of manifestations of agitated behaviors in elderly persons over a 1-week period. The CMAI is a questionnaire consisting of 29 agitated behaviors, each rated on a 7-point frequency scale. In addition to the frequency of each behavior, informants/caregivers will be asked to use a 5-point scale to rate the disruptiveness of each behavior. For this study, the CMAI will target behaviors observed by knowledgeable informants/informed caregivers. Expanded descriptions of the behaviors will be provided to the informant/caregiver to be used as a reference during the interview.	Baseline, Day 7 and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in agitation as measured by the Cohen-Mansfield Agitation Inventory (CMAI) at 12 weeks	The Cohen-Mansfield Agitation Inventory (CMAI) assesses the average frequency of manifestations of agitated behaviors in elderly persons over a 1-week period. The CMAI is a questionnaire consisting of 29 agitated behaviors, each rated on a 7-point frequency scale. In addition to the frequency of each behavior, informants/caregivers will be asked to use a 5-point scale to rate the disruptiveness of each behavior. For this study, the CMAI will target behaviors observed by knowledgeable informants/informed caregivers. Expanded descriptions of the behaviors will be provided to the informant/caregiver to be used as a reference during the interview.	Baseline, Day 7, Day 14, Week 4, Week 8 and Week 12
Clinical Global Impression of Change in Behavior (CGIC-B)	The Clinical Global Impression of Change in Behavior (CGIC-B) is similar to the mADCS-CGIC in that both versions provide a systematic method for assessing clinically significant change in clinical trials as evaluated by an experienced clinician on the basis of a clinical interview and examination. It relies on both direct examination and/or observation of the participant as well as interviews with a knowledgeable informant/informed caregiver. The participant interviews that are a part of the mADCS-GGIC are not feasible in this study population and have been eliminated in the CGIC-B in favor of standard administration across all participants. Anchors present in the mADCS-CGIC that are not relevant in this study population have been removed and agitation-related anchors have been added to the CGIC-B. A skilled and experienced clinician who is blinded to treatment assignment rates the patient on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening).	Baseline, Day 7, Day 14, Week 4, Week 8 and Week 12

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Medical University of South Carolina; National Institute on Aging (NIA); Alzheimer's Therapeutic Research Institute; Alzheimer's Clinical Trials Consortium
• Investigators: Study Director: Paul Aisen, MD, Alzheimer's Therapeutic Research Institute; Principal Investigator: Jacobo Mintzer, MD, Ralph H. Johnson Veterans Affairs Medical Center (VAMC); Principal Investigator: Brigid Reynolds, NP, Georgetown University

Publications and helpful links

Helpful Links

• ATRI Studies Page
• LiBBY Study Website

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: November 16, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: dementia; agitation; alzheimer's disease; hospice care-eligible; agitation and dementia (HAD); alzheimer's disease dementia; alzheimer's disease and related dementias
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Neurobehavioral Manifestations; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Dyskinesias; Psychomotor Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Alzheimer Disease; Dementia; Psychomotor Agitation; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: ATRI-007; R01AG068324 (U.S. NIH Grant/Contract); R01AG095004 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

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.: No