Neural Substrates of Emotion: Impact of Cocaine Dependence

NCT02682784 | Completed Phase 2 Results

• 1 other identifier: PRO39699
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

Over one million individuals in the United States meet criteria for cocaine use disorders. Relapse rates are highest among cocaine-dependent (CD) populations. Social stress is a significant risk factor for relapse. Data from human neuroimaging studies suggest that "top-down" prefrontal cortical inhibition of amygdala activity controls emotional responses to social stimuli. A growing literature suggests that hypoactivity in the medial prefrontal cortex coupled with increases in amygdala activity underscore the vulnerability of CD individuals to relapse. Neuroimaging studies of corticolimbic network activity (functional connectivity) have been conducted in CD subjects at rest. Compared with healthy controls, CD subjects exhibited lower corticolimbic connectivity and the degree of corticolimbic uncoupling was associated with time to relapse. Studies measuring corticolimbic connectivity during exposure to a social stress task in CD subjects could provide critical insight into the neurobiologic mechanisms that underscore the sensitivity of CD individuals to social stress. Moreover interventions that improve corticolimbic connectivity in CD subjects may be effective therapeutic strategies for preventing relapse in CD populations. Oxytocin (OT) is an anxiolytic neuropeptide that attenuates amygdala responses to aversive social cues. In order to better understand the neurobiologic mechanisms that control emotion-related behavior in CD populations, we propose a double-blind placebo (PBO) controlled study using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure (1) corticolimbic functional connectivity during the Montreal Imaging Stress Task (MIST) and (2) amygdala activity in response to an implicit facial affect recognition paradigm in groups of CD individuals (CD n=80) and healthy non-dependent controls (HC, n=80). Prior to the scanning session, participants will receive either intranasal OT (24 IU) or PBO spray (n=40 per treatment group). The order of the tasks will be counterbalanced.

Conditions

Cocaine Use Disorder

Outcome Measures

Primary Outcomes (2)

• Functional Connectivity Between Corticolimbic Brain Regions During Acute Social Stress

  Psychophysiological interaction (PPI) analysis measures how strongly one region of the brain is connected to another brain region during a particular experimental condition, such as doing arithmetic while being given feedback about performance. The strength of this functional connection between two regions can be expressed as a parameter estimate - the higher the value of the parameter estimate, the more strongly connected the two regions are so that as activation in one region increases, activation in the connected region also increases. However, two regions can also be strongly negatively connected such that if activation in one region goes up during a task condition, activation in the other region goes down

  During Montreal Imaging Stress Task in fMRI scanner

• Amygdala Activity in Response to Fearful Faces

  Use an implicit facial affect recognition paradigm to determine the impact of cocaine dependence and oxytocin on amygdala activity in response to fearful faces. The BOLD signal measured during neutral faces will be subtracted from the BOLD signal measured during fearful faces.

  During Facial Recognition Task in fMRI scanner

Study Arms (4)

Oxytocin/Cocaine User

EXPERIMENTAL

Individuals who meet criteria for cocaine use disorder and are randomized to oxytocin.

Drug: Oxytocin

Placebo/Cocaine User

ACTIVE COMPARATOR

Individuals who meet criteria for cocaine use disorder and are randomized to placebo.

Drug: Placebo

Oxytocin/Control

EXPERIMENTAL

Healthy controls who are randomized to oxytocin.

Drug: Oxytocin

Placebo/Control

ACTIVE COMPARATOR

Healthy controls who are randomized to placebo.

Drug: Placebo

Interventions

Oxytocin DRUG

Nasal spray based on naturally occurring hormone, oxytocin.

Also known as: Pitocin

Oxytocin/Cocaine User; Oxytocin/Control

Placebo DRUG

Placebo/Cocaine User; Placebo/Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Age 18-65.
• Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
• Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) for the three-day period immediately prior to the study visit.
• Subjects must consent to random assignment.
• Subjects must have a negative breathalyzer, urine drug screen at the study visit.
• Subjects must consent to the study visit which includes an outpatient visit to the ASD and completing one functional magnetic resonance imaging (fMRI) scanning session.
• Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, or neurological disease including diabetes.
• Subjects with a history of or current psychotic disorder or bipolar affective disorder.
• Subjects with current major depressive disorder or post-traumatic stress disorder.
• Subjects taking any psychotropic medications, including SSRI's or other antidepressants, opiates or opiate antagonists. Subjects taking trazodone or non-benzodiazepene hypnotics for sleep will be included.
• Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
• Subjects who have a BMI that procludes them from fitting comfortably in the scanner.
• Persons with ferrous metal implants or pacemaker.
• Subjects that are claustrophobic.
• Subjects with significant psychiatric or medical problems that would impair participation or limit ability to complete the scanning session.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

MeSH Terms

Interventions

Oxytocin

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Lisa Nunn
• Organization: Medical University of South Carolina

jenkinli@musc.edu

843-792-0476

Study Officials

• Aimee L McRae-Clark, PharmD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2016
• First Posted: February 15, 2016
• Study Start: July 1, 2015
• Primary Completion: July 27, 2020
• Study Completion: July 27, 2020
• Last Updated: October 21, 2021
• Results First Posted: October 21, 2021

Record last verified: 2021-09

Locations

US (1)