Cannabinoids and Traumatic Brain Injury: A Randomized, Placebo Controlled Trial

Brain Injuries, Traumatic Clinical Trial

Official title:

Cannabinoids and Traumatic Brain Injury: A Randomized, Placebo Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05632627
• Other study ID #: 22-1427
• Status: Recruiting
• Phase: Phase 2
• Start date: April 11, 2023
• Est. completion date: December 15, 2025

Study information

• Verified date: January 2024
• Source: University of Colorado, Denver
• Contact: Raeghan Mueller, PhD
• Phone: 3033041805
• Email: raeghan.mueller[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a double-blind, placebo-controlled, parallel group study designed to assess the tolerability and efficacy of fsCBD and bsCBD, compared to a placebo control, to improve cognition and traumatic brain injury-related symptoms. If eligible for the study, subjects will be randomized to receive one of the conditions for 12 weeks.

Description:

To better understand the effects of hemp-derived CBD with and without a small amount of THC, we propose a Phase II randomized clinical trial (RCT) to examine the safety, tolerability, and clinical effects of Full Spectrum CBD (fsCBD, contains less than 0.3% THC) vs. Broad Spectrum CBD (bsCBD, does not contain THC), vs. a matching placebo in a population of patients with traumatic brain injury. This is a double-blind, placebo-controlled, parallel group study designed to assess the tolerability and efficacy of fsCBD and bsCBD, compared to a placebo control, to improve cognition and TBI-related symptoms such as anxiety, pain, depression, and sleep. If eligible for the study, subjects will be randomized to receive one of the conditions for 12 weeks. The initial Week 0 / Baseline visit will take place at the University of Colorado Anschutz Medical Campus. There will be in-person visits at Weeks 1, 6, and 12. Participants will be contacted remotely each remaining week during the 12-week period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 15, 2025
• Est. primary completion date: December 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Ability to provide valid informed consent

2. 18-60 years old

3. Current or history of TBI as identified by the Ohio Identification Method

4. TBI severity is mild or moderate based on the VA/DoD Classification of TBI Severity

5. TBI event must have resulted in hospital evaluation (emergency department or other hospital-based assessment) or evaluation within a clinical setting, except in cases in which the TBI was acquired in a military deployment context in which medical services were not immediately available

6. Ongoing neuropsychiatric symptoms (i.e., depressive, anxiety, pain, cognitive complaints, or sleep complaints) that are plausibly associated with TBI and not better accounted for by co-occurring medical or psychological health conditions

7. Not currently in another treatment study for TBI-related symptoms or co-occurring medical or psychological health conditions

8. Co-occurring treatments must be stable in type, dose, and frequency for the four weeks preceding study enrollment and participants must commit to making no changes in these co-occurring treatments during the study

Exclusion Criteria:

1. Currently incarcerated, paroled, or on probation

2. Participant has retained an attorney in relation to the TBI

3. Pregnant at the time of study enrollment or unwilling to commit to the use of two forms of contraception throughout the duration of the study

4. Vision, hearing, or communication impairments that preclude valid completion of study assessments

5. History of autism spectrum disorders, intellectual disability, and/or serious neurological or central nervous system disease that would be expected to affect cognition (e.g., epilepsy, tumors, multiple sclerosis)

6. Evidence of poor effort (TOMMe < 8) on neuropsychological testing at baseline/Week 0

7. Current or lifetime diagnosis of a schizophrenia spectrum disorder, psychotic disorder, bipolar disorder type I & II, cluster B personality disorders (antisocial, borderline, narcissistic, histrionic), eating disorders, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revised (DSM-5-TR, APA 2022)

8. Meets criteria for major depressive episode as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revised (DSM-5-TR, APA 2022) and with a Beck Depression Inventory-2 score > 24;

9. Current suicidal ideation, as indicated by Beck Depression Inventory-2 item #9 score > 0, or C-SSRS endorsement of item #2, or verbal or written report of current suicidal ideation by the participant to any study team member

10. History of significant systemic illness or unstable medical condition

11. Alcohol use disorder score of 5 or greater, or substance use disorder, based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revised (DSM-5-TR, APA 2022), in the six months preceding study enrollment

12. Reported use of other drugs (cocaine, opiates, methamphetamine, MDMA) in the past 60 days or test positive on a urine test for those drugs of abuse at baseline;

13. Currently taking medications known to be contraindicated with Epidiolex (buprenorphine, leflunomide, levomethadyl acetate, lomitapide, mipomersen, pexidartinib, propoxyphene, sodium oxybate, teriflunomide, clobazam, lamotrigine, valproate).

14. Current diagnosis of a seizure disorder or epilepsy

15. Report using cannabis once daily or more than once daily over the last 12 months

16. Report current use of CBD for medical reasons or TBI symptoms

17. Liver function enzymes (AST, ALT) that are greater than 2x normal

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Wounds and Injuries

Intervention

Drug:
• Cannabidiol
The current study will directly test the hypothesis that a moderate dose of CBD leads to improvements in cognition, TBI-related symptoms, pain, sleep, depression, anxiety, and peripheral markers of inflammation and oxidative stress.
• Placebo
Placebo arm

Locations

Country	Name	City	State
United States	University of Colorado Anschutz	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Colorado State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Neuropsychiatric Symptoms	The effects of study treatment (CBD or placebo) on neuropsychiatric symptoms associated with TBI will be assessed by the Neurobehavioral Symptom Inventory (NSI)	Week 0 to Week 12
Primary	Change in Cognition	The effects of study treatment (CBD or placebo) on attention, processing speed, working memory, long-term memory recall, and executive function will be assessed using the Trail Making Test; the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span, Symbol Search, Coding, Letter-Number Sequencing; and HVLT delayed recall, to create domain scores used to inform an aggregate measure of cognition.	Week 0 to Week 12
Secondary	Change in Biomarkers of Inflammation	Circulating levels of cytokine proteins before and after will be measured using immunoassay before and after treatment	Week 0 to Week 6, Week 0 to Week 12
Secondary	Change in Biomarkers of Oxidative Stress	Circulating levels of cytokine proteins before and after will be measured using immunoassay before and after treatment	Week 0 to Week 12
Secondary	Change in Pain Intensity	PROMIS Pain Intensity 1a - A single-item measure of pain intensity. Average pain in the last 7 days is recorded on a scale of 1 - 10, with higher scores indicating higher pain levels.	Week 0 to 12
Secondary	Change in Anxiety	PROMIS Anxiety SF - An 8-item measure to rate subjective anxiety symptoms. Possible scores range from 1 - 5 with higher scores indicating worse anxiety symptoms.	Week 0 to 12
Secondary	Change in Sleep Disturbance	PROMIS SF v10 Sleep Disturbance 4a - a 4-item measure assessing subjective sleep quality.	Week 0 to Week 6, Week 0 to Week 12
Secondary	Change in Quality of Life	The Short Form 36 will be used to measure quality of life.	Week 0 to Week 12
Secondary	Change in Depression	The Beck Depression Inventory II (BDI-II) will be used to measure depressive symptoms throughout the study.	Week 0 to Week 12