Exercise Facilitation of Adolescent Fear Extinction, Frontolimbic Circuitry, and Endocannabinoids
ConditionAdolescence
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age14-17
SponsorWayne State University
About this trial
Anxiety disorders commonly begin during adolescence, and are characterized by deficits in the ability to inhibit or extinguish pathological fear. Recent research has provided new understanding of how fear is learned and can be regulated in the adolescent brain, and how the endocannabinoid system shapes these processes; however, these advances have not yet translated into improved therapeutic outcomes for adolescents with anxiety. This study will test whether a behavioral intervention, acute exercise, can help to improve fear regulation by enhancing brain activity and endocannabinoid signaling. This line of research may ultimately lead to more effect treatments for adolescent anxiety, and to new preventive strategies for at-risk youth.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and available for the duration of the study
14-17 years of age upon enrollment
Right-handed
Disqualifiers
Traumatic brain injury with ongoing symptoms
Sensory (e.g., hearing) or physical (e.g., motor, balance) impairment or significant developmental delay
MRI participants: MRI contraindication (e.g., braces, implants, claustrophobia)
Any condition that would contraindicate blood draws (e.g., hemophilia, sickle cell)
Trial design
Design model
Parallel
Treatments tested in this trial
Moderate Intensity Exercise
BehavioralParticipants randomized to the active (moderate intensity) exercise condition will complete a 3-minute warm-up at low speed on a treadmill. Speed and incline will be increased in 3-minute increments until moderate-intensity exercise, defined as participants staying within a zone of 60-80% AAMHR with the target being to attain and maintain 70-75% AAMHR while briskly walking and/or jogging depending on current fitness status, is reached for a total of 30 min.
Treatment groups
174 Participants
are divided into 2 treatment groupsGroup A: Moderate Intensity ExerciseExperimental treatment 1 intervention
Group B: Control (Coloring)No intervention 0 interventions
Trial outcomes
Primary outcomes
1
Skin Conductance Responding (SCR)
To compare the effects of acute moderate-intensity exercise (vs. sedentary control) on extinction recall, the investigators will place three electrodes on participant's left hand to acquire SCR data using a BIOPAC MP160 Data Acquisition System (BIOPAC Systems, Inc.).
Time frame
Throughout study completion (3 days)2
Unconditioned Stimulus (US) Expectancy Ratings
US Expectancy Ratings will be measured during fear learning, extinction, and recall tasks
Time frame
Throughout study completion (3 days)3
Fear extinction neural circuitry: Functional activation and coupling
MRI eligible only: fMRI blood-oxygen-level-dependent (BOLD) response will be measured across the entire brain during a test of extinction recall. The investigators will focus on response in the hippocampus and ventromedial prefrontal cortex activation and coupling (gPPI) during recall (CS+E\>CS+U).
Time frame
Neuroimaging will occur during the fear extinction recall phase on Day 34
Endocannabinoid (eCB) Concentrations
Plasma and saliva samples will be collected immediately before and after exercise or sedentary control condition. Samples will be analyzed using liquid chromatography-mass spectrometry to quantify concentrations of eCBs.
Time frame
eCB concentrations will be measured in plasma and saliva immediately before and after the exercise or control condition on Day 2Secondary outcomes
1
Fear Ratings
Fear ratings to each CS will be captured at the beginning, middle, and end of each phase, using a response pad and a 1-5 visual analog scale (1 = not scary at all, 5 = very scary).
Time frame
Throughout study completion (3 days)2
Approach/Avoidance Behavior
The investigators will quantify forward-to-backward response pad distance in virtual meters from the conditioned stimulus.
Time frame
Throughout study completion (3 days)3
Amygdala response during extinction recall
MRI Eligible Only: fMRI blood-oxygen-level-dependent (BOLD) response will be measured across the entire brain during a test of extinction recall. A secondary region of interest is amygdala response during recall (CS+E\>CS+U).
Time frame
Neuroimaging will occur during the fear extinction recall phase on Day 3Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Wayne State University
Lead sponsor
National Institute of Mental Health (NIMH)
Collaborator
Source ClinicalTrials.gov