Investigation of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients.

NCT ID: NCT02255357

Last Updated: 2023-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2018-02-14

Brief Summary

This proposal describes a combined laboratory and clinical trial preliminary investigation to advance medication development for cocaine dependence. The main objective is to test whether intranasal Oxytocin could reduce relapse risk by reducing stress sensitivity. To measure the stress sensitivity, this study will evaluate a new stress challenge: a) Intranasal desmopressin, a vasopressin analog, will be used an endocrine stressor; its effects will be evaluated by serial measurements of serum Adrenocorticotropin hormone (ACTH), and self reports; b) if pretreatment with intranasal oxytocin dampens the ACTH and subjective response to intranasal desmopressin. These measures will be tested during a 7-day inpatient abstinence induction hospitalization. For those patients with family and work obligations, an outpatient abstinence induction procedure is available. The response to the desmopressin challenge will be compared to a cohort of matched control subjects. After abstinence induction, cocaine dependent patients enter a 6-week, double blind, randomized, placebo-controlled trial of 24 IU of intranasal oxytocin vs. placebo, to monitor if this reduces the relapse risk.

Detailed Description

This study is based on the findings that chronic stress, caused in these patients by cocaine dependence, increases the sensitivity of the Hypothalamo-Pituitary-Adrenal (HPA) axis and CNS stress pathways to vasopressin. For their part, oxytocin systems, in chronic stress, acquire an increasing moderating effect on CNS stress system and the HPA axis. Cocaine dependence generates increased responsivity of stress system to oxytocin in the face of depleted oxytocin stores; thus creating an environment where exogenous oxytocin could exert a strong regulatory effect. Intranasal administration provides a convenient method to deliver these small peptides to the brain. Studying the feasibility of this approach, and its applicability to the treatment of cocaine-dependent patients, will be a goal of the study. The main outcome of this study will be the number of consecutive days of abstinence from cocaine after abstinence induction. A secondary outcome will be: Is the acute effect of intranasal oxytocin on desmopressin-induced ACTH secretion associated with the number of days of continued abstinence.

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Solution containing only the excipients of the original solution without Oxytocin.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution containing only the excipients of the original solution without Oxytocin.

Intranasal Syntocinon

Intranasal Oxytocin 24 IU per day.

Group Type: ACTIVE_COMPARATOR

Intranasal Oxytocin

Intervention Type: DRUG

solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm

Interventions

Placebo

Solution containing only the excipients of the original solution without Oxytocin.

Intervention Type: DRUG

Intranasal Oxytocin

solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm

Intervention Type: DRUG

Other Intervention Names

Syntocinon

Eligibility Criteria

Inclusion Criteria

• Age 18 to 60.
• Meet DSM-IV criteria for current cocaine dependence and is seeking treatment.
• Displays at least one cocaine-positive urine toxicology during screening.
• Use of cocaine at least 4 days in the past month, with at least weekly use, or reports episodic binges of large amounts of cocaine (at least $200) at least 2x/month.
• Able to give informed consent and comply with study procedures.
• Can pass the blindfolded scent test recognizing the scent of cinnamon or coffee.

• Age 18 to 60.
• Able to give informed consent and comply with study procedures.
• Can pass the blindfolded scent test recognizing the scent of cinnamon or coffee.

Exclusion Criteria

• History of allergy or adverse event related to Oxytocin or Desmopressin. Patient using Oxytocin or Vasopressin-based products cannot participate.
• Chronic organic mental disorder, insufficient proficiency in English, or any condition or status (illiteracy) that would render an individual incapable of giving informed consent.
• Significant current suicidal risk, suicide attempt within the past year.
• Unstable physical disorders, which might make participation hazardous.
• Coronary Vascular disease as indicated by history, or suspected by abnormal ECG.
• Currently meets DSM-IV criteria for another substance dependence or abuse disorder other than nicotine, or alcohol. If alcohol dependent, must not be in need of detoxification.
• Participants who cannot comply with study procedures during the inpatient or outpatient abstinence induction (phase 1) will not proceed to Phase 2.
• Pregnancy, positive urine pregnancy test, or breastfeeding. Women who wish to participate must agree to use a method of contraception during the study and sign a written commitment to that effect, and submit to a urine pregnancy test every two weeks of Phase 2.
• History of transphenoidal surgery or sinus surgery in the past month. Simple nasal congestion is not exclusionary.

• Unstable physical disorders, which might make participation hazardous.
• Diagnosis of Substance Abuse or Dependence disorder, with exception of nicotine dependence. Patients in remission may participate if its duration is greater than 2 years preceding participation.
• History of allergy or adverse event related to oxytocin or desmopressin. Patient using oxytocin or vasopressin-based products cannot participate.
• Chronic organic mental disorder, insufficient proficiency in English or illiteracy that would render an individual incapable of giving informed consent.
• History of transphenoidal surgery or sinus surgery in the past month. Simple nasal congestion is not exclusionary.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Wilfrid Raby

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wilfrid N Raby, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Substance Abuse, Department of Psychiatry - Columbia university

Locations

Substance Treatment and Research Service (STARS)

Manhattan, New York, United States

Divison on Substance Abuse - Albert Einstein College of Medicine

The Bronx, New York, United States

Countries

United States

References

Araya AV, Rojas P, Fritsch R, Rojas R, Herrera L, Rojas G, Gatica H, Silva H, Fiedler JL. Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment. Endocrine. 2006 Dec;30(3):289-98. doi: 10.1007/s12020-006-0007-2.

Reference Type: BACKGROUND

PMID: 17526941 (View on PubMed)

Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G. Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res. 2008;170:473-512. doi: 10.1016/S0079-6123(08)00437-8.

Reference Type: BACKGROUND

PMID: 18655903 (View on PubMed)

Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21437-41. doi: 10.1073/pnas.0909579106. Epub 2009 Nov 23.

Reference Type: BACKGROUND

PMID: 19934046 (View on PubMed)

Suzuki Y, Yamamoto S, Umegaki H, Onishi J, Mogi N, Fujishiro H, Iguchi A. Smell identification test as an indicator for cognitive impairment in Alzheimer's disease. Int J Geriatr Psychiatry. 2004 Aug;19(8):727-33. doi: 10.1002/gps.1161.

Reference Type: BACKGROUND

PMID: 15290695 (View on PubMed)

Weiss RD, Griffin ML, Hufford C, Muenz LR, Najavits LM, Jansson SB, Kogan J, Thompson HJ. Early prediction of initiation of abstinence from cocaine. Use of a craving questionnaire. Am J Addict. 1997 Summer;6(3):224-31.

Reference Type: BACKGROUND

PMID: 9256988 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.pdr.net/drug-summary/pitocin?druglabelid=1666&mode=preview

Oxytocin description

http://www.pdr.net/drug-summary/ddavp-nasal-spray?druglabelid=1034&mode=preview

Desmopressin Acetate description

Other Identifiers

DA035461-01A1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

#6933

Identifier Type: -

Identifier Source: org_study_id