Investigation of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Solution containing only the excipients of the original solution without Oxytocin. |
Drug: Placebo
Solution containing only the excipients of the original solution without Oxytocin.
|
| Active Comparator: Intranasal Syntocinon Intranasal Oxytocin 24 IU per day. |
Drug: Intranasal Oxytocin
solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Consecutive Weeks of Abstinence From Cocaine After Abstinence Induction [Up to 6 weeks]
Eligibility Criteria
Criteria
Study Inclusion Criteria (cocaine-dependent participants):
-
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.
Study Exclusion Criteria (cocaine-dependent participants):
-
Meets DSM-IV criteria for bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse. Severe depression is an exclusion criteria (Hamilton Depression Scale ≥ 15).
-
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.
Study Inclusion Criteria (healthy volunteers):
-
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.
Study Exclusion Criteria (healthy volunteers):
-
DSM-IV Axis 1 psychiatric diagnosis. Severe Major Depression (Hamilton Depression Scale > 15) is an exclusion criteria.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Divison on Substance Abuse - Albert Einstein College of Medicine | Bronx | New York | United States | 10045 |
| 2 | Substance Treatment and Research Service (STARS) | Manhattan | New York | United States | 10032 |
Sponsors and Collaborators
- New York State Psychiatric Institute
Investigators
- Principal Investigator: Wilfrid N Raby, PhD, MD, Division of Substance Abuse, Department of Psychiatry - Columbia university
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- 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.
- 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. Review.
- 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.
- 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.
- 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.
- #6933
- DA035461-01A1
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Intranasal Syntocinon |
|---|---|---|
| Arm/Group Description | Solution containing only the excipients of the original solution without Oxytocin. Placebo: Solution containing only the excipients of the original solution without Oxytocin. | Intranasal Oxytocin 24 IU per day. Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm |
| Period Title: Overall Study | ||
| STARTED | 11 | 15 |
| COMPLETED | 4 | 5 |
| NOT COMPLETED | 7 | 10 |
Baseline Characteristics
| Arm/Group Title | Placebo | Intranasal Syntocinon | Total |
|---|---|---|---|
| Arm/Group Description | Solution containing only the excipients of the original solution without Oxytocin. Placebo: Solution containing only the excipients of the original solution without Oxytocin. | Intranasal Oxytocin 24 IU per day. Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm | Total of all reporting groups |
| Overall Participants | 11 | 15 | 26 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
11
100%
|
15
100%
|
26
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
27.3%
|
2
13.3%
|
5
19.2%
|
| Male |
8
72.7%
|
13
86.7%
|
21
80.8%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
11
100%
|
14
93.3%
|
25
96.2%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
1
6.7%
|
1
3.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
11
100%
|
15
100%
|
26
100%
|
Outcome Measures
| Title | Number of Consecutive Weeks of Abstinence From Cocaine After Abstinence Induction |
|---|---|
| Description | |
| Time Frame | Up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Intranasal Syntocinon |
|---|---|---|
| Arm/Group Description | Solution containing only the excipients of the original solution without Oxytocin. Placebo: Solution containing only the excipients of the original solution without Oxytocin. | Intranasal Oxytocin 24 IU per day. Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm |
| Measure Participants | 11 | 15 |
| Mean (Inter-Quartile Range) [weeks] |
1.0
|
1.0
|
Adverse Events
| Time Frame | 6 months during randomized trial or participants length of participation | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Placebo | Intranasal Syntocinon | ||
| Arm/Group Description | Solution containing only the excipients of the original solution without Oxytocin. Placebo: Solution containing only the excipients of the original solution without Oxytocin. | Intranasal Oxytocin 24 IU per day. Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm | ||
All Cause Mortality |
||||
| Placebo | Intranasal Syntocinon | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/15 (0%) | ||
Serious Adverse Events |
||||
| Placebo | Intranasal Syntocinon | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/11 (0%) | 0/15 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Intranasal Syntocinon | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/11 (54.5%) | 5/15 (33.3%) | ||
| Gastrointestinal disorders | ||||
| nausea | 1/11 (9.1%) | 1 | 0/15 (0%) | 0 |
| General disorders | ||||
| feeling woozy | 1/11 (9.1%) | 1 | 0/15 (0%) | 0 |
| headache | 3/11 (27.3%) | 3 | 0/15 (0%) | 0 |
| feeling energized | 0/11 (0%) | 0 | 3/15 (20%) | 3 |
| less irritable | 0/11 (0%) | 0 | 1/15 (6.7%) | 1 |
| calm | 0/11 (0%) | 0 | 1/15 (6.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| cough | 1/11 (9.1%) | 1 | 0/15 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | wilfrid raby, m.d. |
|---|---|
| Organization | new york psychiatric institute |
| Phone | 2129233031 |
| wilfrid.raby@nyspi.columbia.edu |
- #6933
- DA035461-01A1