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Oxytocin, Stress, Craving, Opioid Use Disorder (OSCO)

Primary Purpose

Opioid Use Disorder

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
intranasal oxytocin, 40 IU, twice a day for 7 days
Sponsored by
Brown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Use Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female (50%), 18 to 65 (inclusive) years of age;
  • Currently meets DSM-5 criteria for OUD;
  • Currently on a stable dose of buprenorphine/naloxone 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.

Sites / Locations

  • Brown UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

oxytocin

matching placebo

Arm Description

The oxytocin will be formulated at 5mg/0.1mL (5mg/spray) and dispensed as 10-mL nasal spray, twice a day (2 sprays per nostril) for 7 days (total daily dose: 40 international units, IU).

The oxytocin-matched placebo will be formulated at 5mg/0.1mL (5mg/spray) and dispensed as 10-mL nasal spray, twice a day (2 sprays per nostril) for 7 days (total daily dose: 40 international units, IU).

Outcomes

Primary Outcome Measures

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 Opioid Craving Questionnaire (OCQ) the stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the OCQ will be administered 4 times: before starting any procedure, during the yohimbine challenge, at the cue-reactivity and end of experiment. The primary outcome will be the area under the curve (AUC) formed by the OCQ score. This outcome will be compared between oxytocin and matching-placebo during the stress induction produced by yohimbine or matching-placebo.

Secondary Outcome Measures

Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: side effects
Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in reports of side effects (headache, vertigo, edema, nausea, somnolence, anxiety, abdominal pain, palpitations) at the laboratory sessions and at the follow up visit. Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: opiate withdrawal syndrome
Safety measures include: opiate withdrawal syndrome by Clinical Opiate Withdrawal Scale (COWS) that will be monitored during the entire study timeline.
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: anxiety
To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in assessing anxiety using the Hamilton scale. Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: blood pressure (BP)
To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in reports of blood pressure. Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: heart rate (HR)
To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in reports of heat rate (HR). Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)

Full Information

First Posted
August 6, 2019
Last Updated
January 25, 2023
Sponsor
Brown University
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1. Study Identification

Unique Protocol Identification Number
NCT04051619
Brief Title
Oxytocin, Stress, Craving, Opioid Use Disorder
Acronym
OSCO
Official Title
Oxytocin to Reduce Stress-induced Craving in Individuals With Opioid Use Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 6, 2020 (Actual)
Primary Completion Date
December 22, 2023 (Anticipated)
Study Completion Date
December 23, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brown University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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=50 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
oxytocin
Arm Type
Experimental
Arm Description
The oxytocin will be formulated at 5mg/0.1mL (5mg/spray) and dispensed as 10-mL nasal spray, twice a day (2 sprays per nostril) for 7 days (total daily dose: 40 international units, IU).
Arm Title
matching placebo
Arm Type
Placebo Comparator
Arm Description
The oxytocin-matched placebo will be formulated at 5mg/0.1mL (5mg/spray) and dispensed as 10-mL nasal spray, twice a day (2 sprays per nostril) for 7 days (total daily dose: 40 international units, IU).
Intervention Type
Drug
Intervention Name(s)
intranasal oxytocin, 40 IU, twice a day for 7 days
Other Intervention Name(s)
Pitocin
Intervention Description
Adjunct therapy
Primary Outcome Measure Information:
Title
Opioid craving
Description
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 Opioid Craving Questionnaire (OCQ) the stress induction will be done using yohimbine or matching placebo (counterbalanced) during the two laboratory sessions. At each visit the OCQ will be administered 4 times: before starting any procedure, during the yohimbine challenge, at the cue-reactivity and end of experiment. The primary outcome will be the area under the curve (AUC) formed by the OCQ score. This outcome will be compared between oxytocin and matching-placebo during the stress induction produced by yohimbine or matching-placebo.
Time Frame
one week
Secondary Outcome Measure Information:
Title
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: side effects
Description
Participants will complete a laboratory session that includes a battery of medical/physiological/psychological assessments to monitor adverse events. To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in reports of side effects (headache, vertigo, edema, nausea, somnolence, anxiety, abdominal pain, palpitations) at the laboratory sessions and at the follow up visit. Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Time Frame
one week
Title
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: opiate withdrawal syndrome
Description
Safety measures include: opiate withdrawal syndrome by Clinical Opiate Withdrawal Scale (COWS) that will be monitored during the entire study timeline.
Time Frame
one week
Title
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: anxiety
Description
To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in assessing anxiety using the Hamilton scale. Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Time Frame
one week
Title
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: blood pressure (BP)
Description
To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in reports of blood pressure. Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Time Frame
one week
Title
Safety and tolerability of oxytocin and yohimbine in OUD individuals receiving buprenorphine/naloxone: heart rate (HR)
Description
To monitor safety and tolerability during the entire course of the study, we will examine between-group differences (oxytocin, placebo) and during yohimbine administration in reports of heat rate (HR). Reporting of the study results will be of a descriptive nature and presented using summary statistics: number of subjects (n), mean (M), standard deviation (SD) or standard error of the mean (SEM), co-efficient of variation (CV), median, minimum, maximum or frequency distributions (n, %)
Time Frame
one week
Other Pre-specified Outcome Measures:
Title
Stress-related response in OUD individuals receiving buprenorphine/naloxone: salivary cortisol
Description
Cortisol (biomarker for stress level) will be measured at the same 4 time points as the OCQ and so analyses for cortisol will follow those for the primary outcome.
Time Frame
one week
Title
Pain-management response in OUD individuals receiving buprenorphine/naloxone: blood beta-endorphin
Description
Beta-endorphin (biomarker for pain management) will be measured at the beginning of treatment and compared to the end of the study.
Time Frame
one week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female (50%), 18 to 65 (inclusive) years of age; Currently meets DSM-5 criteria for OUD; Currently on a stable dose of buprenorphine/naloxone 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carolina L Haass-Koffler, PHARMD
Phone
401-863-6624
Email
carolina_haass-koffler@brown.edu
Facility Information:
Facility Name
Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02291
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zoe Brown, BS
Phone
401-863-6646
Email
opioid.stress.study@brown.edu@brown.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

Oxytocin, Stress, Craving, Opioid Use Disorder

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