Oxytocin, Stress, Craving, Opioid Use Disorder

Opioid Use Disorder Clinical Trial

— OSCO  

Official title:

Oxytocin to Reduce Stress-induced Craving in Individuals With Opioid Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04051619
• Other study ID #: 1904002426
• Status: Completed
• Phase: Phase 1
• Start date: January 6, 2020
• Est. completion date: December 23, 2023

Study information

• Verified date: April 2024
• Source: Brown University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although stress has long been linked to substance use, craving and relapse, there are no available medications that target stress-induced substance use disorder (SUD). In particular, with the rise in opioid use, there is still a crucial need for developing effective pharmacological treatments that target and integrate the complexity of this disease. The long term goal of this project is to identify the key neuroendocrine pathways that are responsible for stress-induced craving in individuals with opioid use disorder (OUD) in order to better understand how they can be effectively treated.

Description:

The goal of this research is to evaluate whether oxytocin, a hormone with anti-stress properties, dampens the effects of stress and opioid-associated cues on opioid craving and thus may be an effective adjunctive treatment for OUD.

The central hypothesis of this research is that oxytocin will reduce stress-induced opioid craving in patients with OUD treated with buprenorphine/naloxone as opioid replacement therapy (ORT). This hypothesis is based on the model of addiction (Koob, Neuron 2008) in which chronic substance use and stress lead to neurobehavioral counter-adaptations that dysregulate biobehavioral response.

In this double-blind, cross-over, placebo controlled, randomized trial, individuals with OUD (N=20 who are currently receiving treatment with buprenorphine/naloxone or methadone will be randomized to intranasal oxytocin (40 international units, IU) and oxytocin-matched placebo, administered twice/day for 7 days with a minimum of two days between the opposite condition (oxytocin or placebo). On days 5 and 7, and on days 14 and 16, participants will complete two counter-balanced sessions in which they receive yohimbine (32.4 mg) or yohimbine-matched placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 23, 2023
• Est. primary completion date: December 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female (50%), 18 to 70 (inclusive) years of age;

• Currently meets DSM-5 criteria for OUD;

• Currently on a stable dose of buprenorphine/naloxone or methadone for at least 3 months;

• In good health as confirmed by medical history, physical examination and blood work (Liver function within 5x the Upper normal limits (AST/ALT) and renal function within 2x the Lower Normal Limit (bilirubin, creatine clearance).

• Willing to take medication and adhere to the study procedures;- Understand informed consent and questionnaires in English at an 8th grade level;

• Clinical Opiate Withdrawal Scale (COWS) = 0 at study screening and prior laboratory sessions.

Exclusion Criteria:

• Women who are breastfeeding, test positive for pregnancy or are unwilling to use medically-approved birth control;

• Suicide attempts in the last three months;

• Current substance disorder other than marijuana, nicotine and caffeine as assessed by self-report and urine toxicology screen at baseline;

• Current use of medications that may interact with study medications;

• History of hypersensitivity to study medications;

• Clinically significant electrolyte abnormalities, current rhinitis or use of vasoconstricting medications or prostaglandins.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders
• Substance-Related Disorders

Intervention

Drug:
• intranasal oxytocin, 40 IU, twice a day for 7 days
Adjunct therapy

Locations

Country	Name	City	State
United States	Brown University	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Brown University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stress-related response in OUD individuals receiving buprenorphine/naloxone: salivary cortisol	Cortisol (biomarker for stress level) will be measured at the same 3 time points as other measures	one day
Primary	Opioid Craving	The primary outcome will test the effect of oxytocin, compared to placebo, on opioid craving during two laboratory stress induction, paired to a cue reactivity paradigm. The dependent measure for the primary aim is the Desire for Drug Questionnaire (DDQ) the stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions.; At each visit the DDQ will be administered 3 times: before starting any procedure, after the yohimbine challenge, and after the cue-reactivity. This outcome will be compared between oxytocin and matching-placebo during the stress induction produced by yohimbine or matching-placebo.	one day
Secondary	Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: opiate withdrawal syndrome	Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: opiate withdrawal syndrome by Clinical Opiate Withdrawal Scale (COWS) pre and post the laboratory procedures.	one day
Secondary	Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: stress	Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor stress (perceived stress scale , PSS) during lab sessions.	one day
Secondary	Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: anxiety	Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor anxiety (HAMA) during lab sessions.	one day
Secondary	Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: systolic/diastolic blood pressure (BP)	Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor systolic/diastolic blood pressure (SBP/DBP) during lab sessions.	one day
Secondary	Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: heart rate (HR)	Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. Safety measures include: monitor Heart rate (HR) during lab sessions.	one day