Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04629716 |
| Other study ID # |
STUDY00001659 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 23, 2021 |
| Est. completion date |
August 31, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Florida State University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Objective of the Protocol: The primary aim of the current protocol is to examine whether or
not habitual use of medical marijuana affects psychomotor functioning operationalized as
driving performance. Secondary endpoints will examine whether type of medical marijuana used,
frequency, dosage or route of administration is associated with adverse effects. The proposed
study is a prospective repeated measures experimental study designed to test medical
marijuana use as the exposure variable in adults age 50 and older and driving errors in
response time, attention, and executive functions as the primary outcome. Secondary outcomes
include: adverse effects. Participants will complete 3 assessments over a 3 month time
period. The 3 assessment time points are: baseline (T1), prior to starting medical marijuana,
1 month post-medical marijuana initiation (T2), and 3 months post-medical marijuana
initiation (T3). Electronic Medical Review (EMR) will be conducted at baseline, 1, and 3
months. In addition, potentially confounding disease, treatment, and sociodemographic
characteristics will be examined. Data will be collected in a manner that is consistent with
transparent reporting as mandated by CONSORT guidelines. Finite mixture modeling and
generalized linear modeling accounting for individual and group level outcomes will be used
to test the study hypotheses. The investigators propose to enroll 60 adults (n=30 medical
marijuana users and n=30 age, race, sex matched controls) ages 50 and older with
chronic/severe non-malignant pain, which is the most common diagnosis for medical marijuana
users. Primary Endpoint: Thus, the proposed study will test medical marijuana use as the
exposure variable in adults age 50 and older and simulated driving performance (e.g. errors
in response time, attention, and executive functioning tasks that predict on-road
performance) as the primary outcome. Secondary Endpoint: Further, the investigators will
explore the association between medical marijuana use and adverse effects.
Description:
The proposed study is a prospective repeated measures experimental study designed to test
medical marijuana use as the exposure variable in adults age 50 and older and driving errors
in response time, attention, and executive functions as the primary outcome. Secondary
outcomes include: adverse effects. Participants will complete 3 assessments over a 3-month
time period. The 3 assessment time points are: baseline (T1) prior to starting medical
marijuana, 1 month post-medical marijuana initiation (T2), and 3 months post-medical
marijuana initiation (T3). Electronic Medical Review (EMR) will be conducted at baseline, 1
and 3 months. In addition, potentially confounding disease, treatment, and sociodemographic
characteristics will be examined. Data will be collected in a manner that is consistent with
transparent reporting as mandated by CONSORT guidelines. Finite mixture modeling and
generalized linear modeling accounting for individual and group level outcomes will be used
to test the study hypotheses.
Participants will be N=60 adults ages 50 and older who have newly registered with the state
of Florida to obtain medical marijuana (n=30) or age, race, sex matched non-marijuana user
controls (n=30).
Intervention Group Recruitment. Participants will be recruited from Medical Marijuana
Treatment Clinics of Florida's (MMTC) Gainesville location. Recruitment for this study begins
pre-medical marijuana exposure. To obtain medical marijuana in the state of Florida there are
four steps:
- Step 1: Determine Eligibility: Eligibility for medical marijuana use must be determined
by a qualified physician. A patient must first seek treatment from a qualified
physician. MMTC has qualified physicians who determine patient eligibility.
- Step 2: Medical Marijuana Registration: Once the MMTC physician determines the patient
is eligible for medical marijuana, the physician then inputs the patient's information
and the medical marijuana order information into the Medical Marijuana Use Registry.
MMTC physicians complete this process during the eligibility appointment. Recruitment
for the current project begins at step 2 which is prior to any exposure to medical
marijuana. Participants will undergo a brief screen during their visit with the MMTC
physician to determine if they meet eligibility criteria (See Eligibility Criteria in
Human Study Record 1 per new NIH guidelines). Eligibility screening procedures will be
IRB-approved and will not collect any identifying information. Self-report
questionnaires will be use to discern eligibility. Eligibility will be confirmed using
medical records at enrollment. If MMTC patients meet eligibility criteria, they will be
given the opportunity to meet with the study research assistant (RA) to learn more about
the project. Participants will be provided a detailed description of the study, and the
research assistant will obtain permission to follow up with the patient (by phone or
text) in order to track their progress on obtaining their registry identification card.
- Step 3: Medical Marijuana Use Registry Identification Card: Once a physician has input
the patient's information into the Medical Marijuana Use Registry (i.e. step 2), the
patient is able to apply for a medical marijuana card. This process takes approximately
10-14 days. Participants will be instructed to schedule their baseline study visit prior
to obtaining their first dose of medical marijuana. At the baseline appointment the
study staff will obtain informed consent and complete the biobehavioral assessment
measures, and participants will complete their first drive.
- Step 4: Dispensation of Medical Marijuana: Once the patient receives the medical
marijuana card, the patient is then able to fill their first order for medical marijuana
at a dispensary. The Medical Marijuana Use Registry will track patients' dose,
frequency, type of medical marijuana received, and route of administration. After
obtaining their medical marijuana card and filling their first dispensation, the
investigators will track patients through MMTC and follow patients for 3 months post
medical marijuana initiation.
Control Group Recruitment. Control participants will be age, race, and sex matched adults 50
and older with a diagnosis of chronic or severe pain recruited from the community using
flyers/handouts; newspaper/Internet advertisements; in-person lectures and events; and
contact via mail, e-mail, and the infrastructure and support of Oak Hammock at the UF, a
residential retirement community. The investigators will also phone individuals enrolled in
the University of Florida HealthStreet and Clinical and Translational Science Institute's
(CTSI) Integrated Data Repository, a database organizing clinical information across UF
Health's clinical and research programs.
Attrition is a large concern in an observational trial of this rigor. Within the lab, based
on prior experience the investigators anticipate between 15-20% dropout by time point 3.
Therefore, the investigators anticipate recruiting 72 participants (62+20%) in order to
achieve our goal. However, there are numerous strategies that the investigators have used in
the past and will put in place to increase retention.
Test of Aim 1 (Driving Simulator)
Driving Simulator Data will be collected via the kinematic functionality of the high-fidelity
driving simulator (e.g. speed in mph, braking, swerving, lateral lane positioning, etc.) and
also through observing the performance of the driver via a trained evaluator who will use the
playback function of the simulator to scrutinize the errors. The drive will begin with a
5-minute acclimation scenario which is designed to train drivers on aspects of simulator
operation and help them adjust to driving in a simulator. The simulator acclimation drive
addresses lane keeping on straight and curved roads, braking, changing lanes, use of side and
rear-view mirrors, and stopping. After the 5-minute acclimation scenario, the driver will
drive the main drive for 10 minutes. Three scripted events will be randomly presented to the
drivers to control for learning effects.
- Event 1. To assess response time, during the drive a vehicle is pulling out in front of
the driver and the driver's behavior is measured via braking milliseconds (ms) and
swerving (standard deviation {SD} of lateral deviation from center lane).
- Event 2. Next, using an established protocol, during the course of the drives divided
attention (being aware of the traffic and surrounding while focusing on critical
stimulus) is assessed via a triangle appearing on the screen and the participant needing
to press a button (i.e. respond) as soon as they see it (measured in ms and number of
omissions and commissions).
- Event 3. Lastly, executive functions are measured by providing the driver with
instructions before the drive (i.e. to turn into a KFC, pull into a parking bay, and
when it is safe to do so, exit the lot and merge into the flow of traffic (measured via
visual scanning (yes/no) speed regulation (mph over or under the speed limit),
adjustment to stimuli (notice the KFC (yes/no), slow down (mph), signaling (yes/no),
vehicle positioning (buffer around the vehicle yes/no), and gap acceptance (narrow or
tight via ms)69, 70,121-122. Participants will be scored on number of tasks completed
correctly.
Within Subject Analysis. To answer the primary question of this proposal, "Does medical
marijuana use affect driving performance?," the investigators will use repeated measures
ANOVA. The investigators will examine within subject differences on measures at all 3 time
points in order to answer the question of whether medical marijuana impacts response time,
divided attention, and executive functions. Using a repeated measures ANOVA, time will serve
as the independent variable and continuous measures of driving errors (as defined above) as
the outcomes. Power Analysis: The investigators computed the power to detect a medium effect
size of 0.5 standard deviations across groups. Assuming a correlation of 0.2 across the
repeated measures at three time points, the standard deviation of the average of three
measures is 0.683 times the standard deviation of one measure. Therefore, with 30 per group
the investigators can detect a difference in this average of 0.5 times the standard deviation
of one measure, using a two-sided test with 80% power. The investigators calculated Cohen's d
using Dr. Classen's prior work that examined total driving errors and specific errors (lane
maintenance) in healthy controls (M=24.08 SD=12.38) and (M=5.78 SD=4.26) versus Parkinson's
patients (M=31.99 SD=22.01) and (M=10.23 SD=9.26), which yielded a Cohen's d of .46-.65
(medium effect size)59; therefore, the investigators will be powered to detect this medium
effect size.
Between Group Analyses Comparisons between medical marijuana users and control group
participants will be examined using independent samples t-test (controlling for unequal
variances using Levene's test) or Mann-Whitney U tests if the data are nonparametric in order
to rule out change over time as an explanation of findings. No difference is hypothesized
between groups at baseline. At time 2 and 3 the control group is hypothesized to have higher
average response time, divided attention reaction time, and scores on divided attention tasks
completed correctly than medical marijuana users.
Test of Aim 2 (Adverse Effects) Adverse Effects. In this study, adverse effects are defined
as undesired effects that occur when medication is administered. The investigators will use
Scripted Prompting, a proactive form of adverse effect capture recognized in the field. This
method is designed to elicit adverse effects without biasing the patient; it is a
standardized question that allows participants to report important symptoms without being
influenced by suggestion. For this study the investigators will ask: "Since initiating
medical marijuana, are you having any problems related to use?"
To describe factors associated with adverse effects, the investigators will report the number
of adverse effects reported by participants at time points 2 and 3. Adverse Effects will be
defined as both a count variable and a binary variable such that absence or presence of
adverse effects will be coded as 0/1 respectively. The investigators will then use Poisson
and Logistic regression methods to examine analyze the bivariate association between dosage,
frequency of use, route of administration (pills, vape, etc.), and type of product (THC v.
CBD). Power Statement: The goal of aim 2 is to examine the strength of the association
between factors of medical marijuana use and adverse effects. Currently, the literature does
not contain data regarding the strength of the association between medical marijuana use and
adverse effects or how dosage, frequency of use, and route of administration are associated
with adverse effects. As there may be insufficient power for statistical significance using
the proposed analyses above, effect size estimates will be used to examine the strength of
the association between variables. With 30 per group, the investigators can detect a
difference of 0.73 standard deviations using a two-sided test with 80% power.
Exploratory Aim: Examine factors associated with study feasibility (enrollment and retention)
for development of a future R01. The investigators will describe the association between
socio-demographic factors (i.e. gender, race, and education) and enrollment and retention in
the intervention condition in order to identify ways to improve study feasibility. The
investigators will use chi-square for dichotomous variables and Pearson correlations for
continuous variables to examine associations between sociodemographic factors and study
enrollment (number screened who meet criteria versus number enrolled) and retention (number
enrolled versus number completing all 3 time points). This method will allow us to identify
candidate predictors of enrollment and attrition to inform the investigative team about
strengthening recruitment/retention efforts for specific subgroups.
