Cocaine Dependence
Conditions
Keywords
Oxytocin, Vasopressin, Cocaine
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.
Interventions
DRUGPlacebo
Solution containing only the excipients of the original solution without Oxytocin.
DRUGIntranasal Oxytocin
solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weeks of Abstinence From Cocaine | Phase 1: 7 days; Phase 2: 6 weeks | this is outcome for the phase 2, clinicial trial portion of this combined laboratory and clinical trial laboratory human study For the human laboratory study, Phase 1, the primary outcome is differences in ACTH levels following a) Intranasal Desmopressin, and, on a consecutive day, b) Intranasal Desmopressin preceded by a treatment with Intranasal Oxytocin (Syntocinon). this takes place on 2 consecutive days |
Countries
United States
Participant flow
Pre-assignment details
For control participants, reasons for not being included in the final analysis included: 1) not completing the laboratory protocol (phase 1) the only portion of the study that they participated in. 2 did not complete, and 1 was excluded for medical complication during the laboratory challenge. For Cocaine use disorder patients, reasons for not included in the analysis or not counting as completers: 1) droping out after the initial inpatient laboratory phase;
Participants by arm
| Arm | Count |
|---|---|
| Placebo Solution containing only the excipients of the original solution without Oxytocin.
Placebo: Solution containing only the excipients of the original solution without Oxytocin. | 14 |
| Intranasal Syntocinon Intranasal Oxytocin 24 IU per day.
Intranasal Oxytocin: solution containing Oxytocin 6 IU/0.1cc or per puff is used in this arm | 29 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 10 | 24 |
Baseline characteristics
| Characteristic | Placebo | Intranasal Syntocinon | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 29 Participants | 43 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 27 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 14 participants | 29 participants | 43 participants |
| Sex: Female, Male Female | 3 Participants | 10 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 19 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 15 |
| other Total, other adverse events | 6 / 11 | 5 / 15 |
| serious Total, serious adverse events | 0 / 11 | 0 / 15 |
Outcome results
Primary
Weeks of Abstinence From Cocaine
this is outcome for the phase 2, clinicial trial portion of this combined laboratory and clinical trial laboratory human study For the human laboratory study, Phase 1, the primary outcome is differences in ACTH levels following a) Intranasal Desmopressin, and, on a consecutive day, b) Intranasal Desmopressin preceded by a treatment with Intranasal Oxytocin (Syntocinon). this takes place on 2 consecutive days
Time frame: Phase 1: 7 days; Phase 2: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo for Phase 2, Clinical Trial | Weeks of Abstinence From Cocaine | 1.0 weeks |
| Intranasal Syntocinon for Clinical Trial Phase 2 | Weeks of Abstinence From Cocaine | 1.0 weeks |