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Effects of Delta9-tetrahydrocannabinol (THC) on Retention of Memory for Fear Extinction Learning in PTSD: R33 Study

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ClinicalTrials.gov Identifier: NCT04080427
Recruitment Status : Not yet recruiting
First Posted : September 6, 2019
Last Update Posted : September 6, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Christine A. Rabinak, Wayne State University

Brief Summary:
The goal of this study is to look at how a type of drug called cannabinoids are related to the processing of fear signals, the experience of emotions and fear, and the pattern of activity in the brain that is involved in these processes and how this relates to the treatment of post-traumatic stress disorder (PTSD). PTSD is an anxiety disorder that occurs after experiencing a traumatic event(s) and is characterized by unwanted memories of the trauma(s) through flashbacks or nightmares, avoidance of situations that remind the person of the event, difficulty experiencing emotions, loss of interest in activities the person used to enjoy, and increased arousal, such as difficulty falling asleep or staying asleep, anger and hypervigilance. The information gained from this study could lead to the development of new treatments for persons who suffer from anxiety or fear-based disorders.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Drug: Placebo capsule Drug: Dronabinol 7.5 milligram oral capsule Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of THC on Retention of Memory for Fear Extinction Learning in PTSD: R33 Study
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Dronabinol

Arm Intervention/treatment
Placebo Comparator: Placebo capsule

In a randomized, double-blind, placebo-controlled, between-subjects design, we will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall.

Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).

Drug: Placebo capsule
Placebo is administered just prior to weekly exposure sessions by the oral route and contains only dextrose in opaque capsules.
Other Name: sugar pill

Experimental: Dronabinol 7.5 milligram oral capsule

In a randomized, double-blind, placebo-controlled, between-subjects design, we will administer a single oral dose of dronabinol (7.5mg) or placebo (PBO) approximately two hours prior to each weekly exposure session (up to 9 sessions) in a standard prolonged exposure treatment protocol comprising 12 session overall.

Half of the participants will receive 7.5mg dronabinol (n=50) and the other half of the participants will receive placebo (n=50).

Drug: Dronabinol 7.5 milligram oral capsule
Dronabinol (7.5mg) is administered just prior to weekly exposure sessions by the oral route and is placed in an opaque capsule with dextrose filler.
Other Name: Marinol




Primary Outcome Measures :
  1. Brain Measures [ Time Frame: Through study completion, an average of 3 months. ]
    functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) percent signal change within region of interests [amygdala; ventromedial prefrontal cortex; hippocampus]

  2. Psychophysiology [ Time Frame: Through study completion, an average of 3 months. ]
    Skin conductance response (SCR): change in SCR [peak amplitude from 0.5-4.5 sec following stimulus presentation minus average 2 second baseline prior to stimulus presentation].

  3. Expectancy Ratings [ Time Frame: Through study completion, an average of 3 months. ]
    To assess the change in expected likelihood that an aversive cue (e.g. noise burst or shock) will occur or not based on while slide was shown, participants will repeatedly rate their expectancy of the aversive cue using a button box on a scale from 1 to 3 [1 = certain that the aversive cue will be presented; 2 = certain that the aversive cue will not be presented; 3 = uncertain whether the aversive cue will be presented].

  4. PTSD Checklist (PCL-5) [ Time Frame: Through study completion, an average of 3 months. ]
    To track PTSD symptom change for each participant. The PCL-5 is a 20-item questionnaire. The self-report rating scale is 0-4 for each symptom: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely", respectively. A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items.

  5. Clinician Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5) [ Time Frame: Through study completion, an average of 3 months. ]
    To track PTSD symptom change for each participant. The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview . In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). The assessor combines information about frequency and intensity of an item into a single severity rating. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. Similarly, CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster.

  6. Subjective Units of Distress Scale (SUDS) [ Time Frame: Through study completion, an average of 3 months. ]
    To assess the change in level of distress from 0 to 100 when facing fears. The higher the number on the scale the more severe the level of distress experienced.


Secondary Outcome Measures :
  1. Visual Analogue Scale of Mood (VAS) [ Time Frame: Through study completion, an average of 3 months. ]
    Subjective ratings of mood and drug effects on a 0-100. Higher numbers on the scale reflect stronger experiences of different mood and drug effects. Each item is scored individually. There is no overall score.

  2. Drug Effects Questionnaire (DEQ) [ Time Frame: Through study completion, an average of 3 months. ]
    Subjective ratings of drug effects on from 1-5 on the following scales: "Feel", "High", and "Like".

  3. Addiction Research Center Inventory (ARCI) [ Time Frame: Through study completion, an average of 3 months. ]
    A standardized questionnaire of 53 statements for assessing subjective effects of psychoactive drugs. Used to differentiate drug effects from placebo. Participants rate "true" if the statement applies to them or "false" if it does not apply. Specific statements are related to a particular drug class and for that drug class all "true" responses are summed for a total score in that drug class. Higher scores means higher subjective drug effects for particular drug classes.

  4. State-Trait Anxiety Inventory (STAI) [ Time Frame: Through study completion, an average of 3 months. ]
    Measures of state and trait anxiety. The STAI has 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: "I am tense; I am worried" and "I feel calm; I feel secure." Trait anxiety items include: "I worry too much over something that really doesn't matter" and "I am content; I am a steady person." All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.

  5. End of Session Questionnaire (ESQ) [ Time Frame: Through study completion, an average of 3 months. ]
    Includes 5 questions total. The first two question ask the participant to select one of several statements that best describes the effect of the capsule they took during that visit. The second question asks the participant to guess what they thought they received in the capsule and how confident they are. The third question asks the participant to rate how much the liked or disliked the effects of the capsule overall on a scale from -5 to 5, with -5 being "disliked a lot", 0 being "neutral", and 5 being "liked a lot". The fourth question asks participants to check "yes" or "no" if they would take the capsule again. Finally, the last question is a free text response asking the participant if they experienced any unusual reactions or if they have any comments or observations that may be relevant to the study.

  6. Heart Rate [ Time Frame: Through study completion, an average of 3 months. ]
    Heart rate

  7. Blood Pressure [ Time Frame: Through study completion, an average of 3 months. ]
    Systolic and diastolic blood pressure will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between ages 18-60
  • Willing and able to consent to study
  • Generally medically and neurologically healthy (including no evidence of intellectual disability or serious cognitive impairment that would interfere with task performance)
  • Exposure to Criterion A stressor defined by CAPS-5 and identified by Life Events Checklist-5 (LEC-5)
  • Significant PTSD severity as indicated by CAPS-5 diagnosis and/or score >= 25 of at least one month prior to study entry, PTSD is patient's primary concern

Exclusion Criteria:

  • Positive urine pregnancy test prior to fMRI, self-reported current pregnancy during screening, or planning pregnancy
  • Currently breastfeeding/ lactating
  • MRI contraindications (e.g., ferrous metal in head/body)
  • Pervasive development disorder history
  • Traumatic brain injury (TBI) with current cognitive impairment related to TBI
  • Risk of harm to self or others that requires immediate intervention
  • Presence of contraindications, current or past allergic or adverse reaction, or known sensitivity to cannabinoid-like substances (dronabinol/marijuana/cannabis/THC, cannabinoid oil, sesame oil, gelatin, glycerin, and titanium dioxide)
  • Lack of fluency in English
  • Inability to tolerate small, enclosed spaces without anxiety (e.g. claustrophobia
  • Exclusively left-handed (score of -100 on Handedness Questionnaire)
  • Current or past diagnosis of bipolar, schizophrenia spectrum, psychotic and related disorders
  • Current severe alcohol or substance use
  • Comorbid mood or anxiety disorder that is primary to PTSD
  • Concomitant treatment with medication taken daily that has level 1 evidence indicating severe drug-drug interactions with dronabinol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04080427


Contacts
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Contact: Allesandra Iadipaolo 313-577-5404 allesandra.iadipaolo@wayne.edu

Locations
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United States, Michigan
Eugene Applebaum College of Pharmacy and Health Sciences
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Wayne State University
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Christien A Rabinak, PhD Wayne State University

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Responsible Party: Christine A. Rabinak, Associate Professor & Principal Investigator, Wayne State University
ClinicalTrials.gov Identifier: NCT04080427     History of Changes
Other Study ID Numbers: R33MH111935
R61MH111935 ( U.S. NIH Grant/Contract )
First Posted: September 6, 2019    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes
Additional relevant MeSH terms:
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Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Dronabinol
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists