Investigation of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients.
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric, Pulmonary |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 11/2/2018 |
| Start Date: | March 2015 |
| End Date: | February 14, 2018 |
Investigation of the Effect of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients
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.
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.
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.
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 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.
We found this trial at
2
sites
Bronx, New York 10045
Phone: 718-409-9450
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Manhattan, New York 10032
Principal Investigator: Wilfrid N Raby, PhD, MD
Phone: 212-740-7311
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