Validation of the Drug Impaired Driving Scenario (DIDS) on the CRCDS-miniSim

NCT04970342 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 202105389
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Subjects will participate in a 4-visit study protocol at the National Advanced Driving Simulator, part of the University of Iowa, in which they will be asked to complete assorted questionnaires, computerized cognitive tasks, and a simulator drive. Subjects will be administered 0.75 mg alprazolam (Xanax) or placebo and 500 mg vaporized cannabis (6.18% THC / \<0.025% CBD) or placebo (0% THC / 0% CBD). The primary objective of this study is to validate the Drug Impaired Driving Scenario (DIDS) using the CRCDS-2 driving simulator by assessing the acute effects of cannabis relative to placebo on simulated driving performance. Assay sensitivity will be demonstrated by the significant effect of 0.75 mg alprazolam (active comparator) on driving and cognitive endpoints.

Conditions

Driving Behavior; Driving Under the Influence

Keywords

Driving; Cannabis; Xanax; Marijuana; Alprazolam; Driving Impairment; Substance Use; SDLP; CogScreen; CRCDS

Outcome Measures

Primary Outcomes (1)

• Standard Deviation of Lateral Position (SDLP)

  The ability to keep the vehicle straight in the lane. Data is presented from the a rural drive with a concurrent divided attention task.

  over one hour during the course of the simulator drive conducted 45 minutes post-dose at Treatment Visit 1, 2, and 3

Secondary Outcomes (1)

• Lane Exceedences

  over one hour during the course of the simulator drive conducted 45 minutes post-dose at Treatment Visit 1, 2, and 3

Study Arms (3)

"Sober" or Double Placebo

EXPERIMENTAL

Subject receives alprazolam capsule containing placebo (lactose). Subject receives placebo cannabis (0% THC / 0% CBD).

Drug: Placebo (Lactose) Capsule; Drug: Cannabis (0%/ THC / 0% CBD)

Active Alprazolam (Xanax), Placebo Cannabis

EXPERIMENTAL

Subject receives active 0.75 mg alprazolam capsule. Subject receives placebo cannabis (0% THC / 0% CBD).

Drug: 0.75 mg Alprazolam Capsule; Drug: Cannabis (0%/ THC / 0% CBD)

Placebo Alprazolam (Xanax), Active Cannabis

EXPERIMENTAL

Subject receives alprazolam capsule containing placebo (lactose). Subject receives active cannabis (6.18% THC / \<0.025% CBD).

Drug: Placebo (Lactose) Capsule; Drug: Cannabis (6.18% THC / <0.025% CBD)

Interventions

Placebo (Lactose) Capsule DRUG

Single dose on two of the three study visits, orally administered 40 minutes prior to cannabis dose

Also known as: Placebo, Placebo Alprazolam

"Sober" or Double Placebo; Placebo Alprazolam (Xanax), Active Cannabis

0.75 mg Alprazolam Capsule DRUG

Single dose on one of the three study visits, orally administered 40 minutes prior to cannabis dose

Also known as: Xanax, Active Alprazolam, Active Xanax

Active Alprazolam (Xanax), Placebo Cannabis

Cannabis (6.18% THC / <0.025% CBD) DRUG

Cannabis vapor is produced from 500 mg of dried plant material (6.18% THC / \<0.025% CBD). Subjects will inhale using the Foltin Puff Procedure over 10 minutes. Single inflated bag/dose consumed via inhalation 40 minutes after alprazolam dose on one of the three study visits.

Also known as: Marijuana, Marihuana, Active Cannabis

Placebo Alprazolam (Xanax), Active Cannabis

Cannabis (0%/ THC / 0% CBD) DRUG

Cannabis vapor is produced from 500 mg of dried plant material (0% THC / 0% CBD). Subjects will inhale using the Foltin Puff Procedure over 10 minutes. Single inflated bag/dose consumed via inhalation 40 minutes after alprazolam dose at two of the three study visits.

Also known as: Marijuana, Marihuana, Placebo Cannabis, Placebo

"Sober" or Double Placebo; Active Alprazolam (Xanax), Placebo Cannabis

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Understands and provides written informed consent prior to the initiation of any protocol-specific procedures.
• Able to comprehend and willing to comply with the requirements of the protocol.
• Healthy male or female adult, 19 to 45 years of age, inclusive, at Screening.
• Regular sleep pattern (usual bedtime between 21:00 and 00:00).
• Score \<10 on Epworth Sleepiness Scale at Screening.
• Able to reliably perform study assessments at Screening (On practice scenario, SDLP no higher than 1 standard deviation greater than the mean for normal healthy adults completing the practice scenario and subject has 7 or more correct hits on the Divided Attention task; CogScreen SDC Correct no less than 1 standard deviation below the mean for healthy adults); demonstrates the ability to understand task instructions at Screening; and is physically (e.g., adequate manual dexterity, vision, and hearing) and cognitively capable of performing study tasks at Screening.
• Possesses (and is willing to provide) a valid driver's license and is an active driver.
• Determined to be (by self-report) an active cannabis user with use of at least once per month over the preceding 90 days.
• Willing to abstain from cannabis use (other than study drug) beginning at the end of Screening until discharge from NADS on Day 2 of Treatment Period 3.
• Female subjects must meet one of the following criteria: 1) If of childbearing potential, female subjects agree to use two contraceptive regimens or remain abstinent during the study; or 2) if of non-childbearing potential, female subjects should be surgically sterile or in a menopausal state.

You may not qualify if:

• A significant history and/or presence of hepatic, renal, cardiovascular, pulmonary, neurological, psychiatric, gastrointestinal, hematological, immunologic, ophthalmologic, metabolic, or oncological disease, or any other medical issue that would, in the opinion of the Investigator, present undue risk for the subject in the study.
• A history of suicidal behavior within 24 months of Screening, has answered YES to questions 3, 4, or 5 on the C-SSRS at Screening or at any clinic admission, or is currently at risk of suicide in the opinion of an Investigator.
• A recent history (within 6 months prior to Screening) of substance use disorder (including alcohol) (as judged by the Investigator) or regularly consumes \>2 alcoholic drinks/day during the last 3 months prior to Screening (1 alcoholic drink is approximately equivalent to: beer \[284 mL\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]). Subjects who consume 3 drinks per day but less than 14 drinks per week may be enrolled at the discretion of the Investigator.
• Demonstrates simulator sickness questionnaire scores which are indicative of simulator sickness as defined in the driving simulation operations manual.
• Regularly consumes excessive amounts of caffeine, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day.
• Smokes more than 10 cigarettes or e-cigarettes, or 3 cigars or pipes per day, or is unable to refrain from smoking during study visits.
• Has been exposed to an investigational drug or device within the 30 days, or 5 half lives (if known), whichever is longer, prior to Screening.
• Has used a prescription or over-the-counter medication known to cause sedation within 7 days prior to Admission for Period 1 and is unwilling or unable to refrain from sedating medication use during study participation.
• Has used any benzodiazepine, barbiturate, or GABAA modulator (e.g., eszopiclone, zopiclone, zaleplon, and zolpidem) within 28 days prior to Admission for Period 1 or is unwilling or unable to refrain from medication use during study participation.
• Has a history of hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV) antibodies 1 or 2.
• Is pregnant or breastfeeding at Screening or any clinic admission or will attempt to become pregnant at any time during study participation.
• Has a clinically significant abnormal finding on 6-lead electrocardiogram (ECG) at Screening or at any clinic admission. The ECG may be repeated once for confirmatory purposes if initial values obtained exceed the limits specified.
• Has a positive urine test for drugs of abuse (other than tetrahydrocannabinol (THC)) or Breath Alcohol Concentration (BrAC) \> 0.0 at Screening or any admission.
• Has any clinically significant abnormal physical examination finding at Screening or any clinic admission.
• Participates in night shift work.

Sponsors & Collaborators

• Timothy L. Brown: lead
• National Highway Traffic Safety Administration (NHTSA): collaborator
• Acclaro Research Solutions, Inc.: collaborator
• Cognitive Research Corporation: collaborator

Study Sites (1)

National Advanced Driving Simulator

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Driving Under the Influence; Marijuana Abuse; Substance-Related Disorders

Interventions

Lactose; Capsules; Alprazolam; nabiximols; Dronabinol

Condition Hierarchy (Ancestors)

Criminal Behavior; Behavior; Dangerous Behavior; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Dosage Forms; Pharmaceutical Preparations; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Timothy Brown, Ph.D.
• Organization: National Advanced Driving Simulator, University of Iowa

timothy-l-brown@uiowa.edu

3193354785

Study Officials

• Timothy L Brown

  National Advanced Driving Simulator, University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study Site/National Advanced Driving Simulator: Triple (Participant, Investigator, Outcomes Assessor) blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Drugged Driving Research

Model Details: The study uses two treatments - alprazolam and cannabis - and placebo. Subjects are randomized to a study sequence where the order of treatments (study arm) is counter-balanced, but all treatments and placebo are received by all subjects. At a visit, you might receive placebo alprazolam and placebo cannabis, placebo alprazolam and active cannabis, or active alprazolam and placebo cannabis. There is not a visit where you receive both active alprazolam and active cannabis.

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: July 21, 2021
• Study Start: July 16, 2021
• Primary Completion: August 21, 2021
• Study Completion: August 21, 2021
• Last Updated: July 25, 2023
• Results First Posted: July 25, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)