Use of Intranasal Oxytocin During Detoxification of Crack Cocaine

Randomized, Double-Blind, Placebo Controlled Study of Intranasal Oxytocin During Detoxification of Crack Cocaine

Randomized treatment control trial, double-blind, parallel, with two arms including ninety-six hospitalized women between 18 and 52 years. Those who agree to participate in the study and meet the eligibility criteria will be randomly allocated to one of the following experimental conditions:

• Conventional oxytocin treatment (T + OC): 32 female cocaine users hospitalized for detoxification will receive six 4 IU jets of intranasal oxytocin twice daily (daily dose of 48 IU) as adjunctive treatment to conventional treatment from the eighth to seventeenth day of hospitalization (duration of oxytocin treatment of 10 days). Conventional treatment includes supportive individual and group psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy as needed to relieve the symptoms of anxiety, aggression and agitation typical of withdrawal and care. 21 days of hospitalization.
• Conventional treatment with placebo administration (T + PBO): 32 female cocaine users hospitalized for detoxification will receive six jets of placebo solution (2% odor-generating propolis essence + the same vehicle as intra-nasal oxytocin: 0.05% citric acid, 0.9% sodium chloride, 1% glycerol, 0.54% disodium phosphate, 0.2% methylparaben + propylparaben, 1% sorbitol, 80% water) twice daily as adjunctive treatment to conventional treatment from the eighth to the seventeenth day of hospitalization (duration of placebo treatment of 10 days). Conventional treatment includes supportive individual and group psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy as needed to relieve the symptoms of anxiety, aggression and agitation typical of withdrawal and care. 21 days of hospitalization.
• Conventional treatment (T): 32 female cocaine users hospitalized for detoxification will receive conventional treatment including individual and group supportive psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy if needed for symptom relief. anxiety, aggression and agitation, typical of abstinence and nursing care, during 21 days of hospitalization.

Outcomes: Withdrawal symptoms, Anxiety symptoms and Depressive symptoms

Study Overview

• Status: Unknown
• Conditions: Cocaine-Related Disorders; Cocaine Withdrawal; Cocaine Smoking
• Intervention / Treatment: Drug: Oxytocin nasal spray; Drug: placebo nasal spray

Detailed Description

Design: Randomized treatment control trial, double-blind, parallel, with two arms.

Sample: Ninety-six hospitalized women between 18 and 52 years will participate in this study. Those who agree to participate in the study and meet the eligibility criteria will be randomly allocated to one of the following experimental conditions:

• Conventional oxytocin treatment (T + OC): 32 female cocaine users hospitalized for detoxification will receive six 4 IU jets of intranasal oxytocin twice daily (daily dose of 48 IU) as adjunctive treatment to conventional treatment from the eighth to seventeenth day of hospitalization (duration of oxytocin treatment of 10 days). Conventional treatment includes supportive individual and group psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy as needed to relieve the symptoms of anxiety, aggression and agitation typical of withdrawal and care. 21 days of hospitalization.
• Conventional treatment with placebo administration (T + PBO): 32 female cocaine users hospitalized for detoxification will receive six jets of placebo solution (2% odor-generating propolis essence + the same vehicle as intra-nasal oxytocin: 0.05% citric acid, 0.9% sodium chloride, 1% glycerol, 0.54% disodium phosphate, 0.2% methylparaben + propylparaben, 1% sorbitol, 80% water) twice daily as adjunctive treatment to conventional treatment from the eighth to the seventeenth day of hospitalization (duration of placebo treatment of 10 days). Conventional treatment includes supportive individual and group psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy as needed to relieve the symptoms of anxiety, aggression and agitation typical of withdrawal and care. 21 days of hospitalization.
• Conventional treatment (T): 32 female cocaine users hospitalized for detoxification will receive conventional treatment including individual and group supportive psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy if needed for symptom relief. anxiety, aggression and agitation, typical of abstinence and nursing care, during 21 days of hospitalization.

Inclusion Criteria:

• Volunteers (no payment to be enroll in the research according with Brazilian legislation)
• Age 18-52 years
• Primary diagnosis of cocaine crack dependence according to DSM-5
• Sex feminine
• Participants must be abstinent at least 7 days prior the study intervention
• Participants must consent to be randomly allocated to experimental conditions

Exclusion Criteria:

• Pregnancy
• Puerperium
• Breastfeeding
• Menopause
• Currently using hormone therapy
• Total hysterectomy
• Diagnosis or suspicion of autoimmune or neurological diseases and / or syndromes (stroke, Parkinson and Alzheimer's)
• Diagnosis or suspected current decompensated and / or severe endocrine, cardiovascular, pulmonary, renal, gastrointestinal disorders
• Moderate or severe psychotic syndrome
• Obesity Level III
• Intellectual impairment (IQ <70)
• Corticosteroid therapy, glucocorticoid or any exogenous steroid therapy
• Infectious condition or acute febrile syndrome
• Significant nasal congestion
• Type III nasal septum deviation (cases considered severe with deviated septum in which breathing is impaired)
• Mucosal lesions
• History of head trauma moderate or severe (Glasgow <12)
• HIV +

Primary Outcome Measure:

1. Withdrawal symptoms Change from baseline withdrawal symptoms (hospital admission) at the end of detoxification treatment (21 days) assessed by Cocaine Selective Severity Assessment (CSSA, minimum and maximum scores: 0 - 112). After treatment, the oxytocin-treated group is expected to have significantly lower withdrawal scores (better outcome) than the other groups (30%).
2. Anxiety symptoms Change from baseline anxiety symptoms (hospital admission) at the end of detoxification treatment (21 days) assessed by the Patient-Reported Outcomes Measurement Information System Short Form scale (PROMIS, minimum and maximum raw scores: 8 - 40). After treatment, the oxytocin-treated group is expected to show lower anxiety scores (better outcome) compared to the other groups (30%).
3. Depression symptoms Change from baseline depressive symptoms (hospital admission) at the end of detoxification treatment (21 days) assessed by the Quick Inventory of Depressive Symptomatology Self-Report scale (QIDS-SR, minimum and maximum scores: 0 - 27). After treatment, the oxytocin-treated group is expected to show lower depressive scores (better outcome) compared to the other groups (30%).

Secondary Outcome Measures:

1. Neuroleptic Dose Change Dose change of neuroleptic medications used during hospitalization for agitation or irritability (expected 25% lower).
2. Adherence of outpatient treatment Rate of adherence of outpatient treatment six months after discharge (expected to be 20% higher) assessed by reviewing the medical records of each patient within the outpatient program. If patient would be enrolled in the outpatient program after six months from detoxification she will be considered adhered to the program (higher rates means better outcome).

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 91720-440
      • Recruiting
      • Hospital Santa Ana
      • Contact: João Vitor Nobrega, MD
      • Principal Investigator: Rodrigo Grassi-Oliveira, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Volunteers (no payment to be enroll in the research according with Brazilian legislation)
• Age 18-52 years
• Primary diagnosis of cocaine crack dependence according to DSM-5
• Sex feminine
• Participants must be abstinent at least 7 days prior the study intervention
• Participants must consent to be randomly allocated to experimental conditions

Exclusion Criteria:

• Pregnancy
• Puerperium
• Breastfeeding
• Menopause
• Currently using hormone therapy
• Total hysterectomy
• Diagnosis or suspicion of autoimmune or neurological diseases and / or syndromes (stroke, Parkinson and Alzheimer's)
• Diagnosis or suspected current decompensated and / or severe endocrine, cardiovascular, pulmonary, renal, gastrointestinal disorders
• Moderate or severe psychotic syndrome
• Obesity Level III
• Intellectual impairment (IQ <70)
• Corticosteroid therapy, glucocorticoid or any exogenous steroid therapy
• Infectious condition or acute febrile syndrome
• Significant nasal congestion
• Type III nasal septum deviation (cases considered severe with deviated septum in which breathing is impaired)
• Mucosal lesions
• History of head trauma moderate or severe (Glasgow <12)
• HIV +

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional oxytocin treatment (T + OC); 32 female cocaine users hospitalized for detoxification will receive six 4 IU jets of intranasal oxytocin twice daily (daily dose of 48 IU) as adjunctive treatment to conventional treatment from the eighth to seventeenth day of hospitalization (duration of oxytocin treatment of 10 days). Conventional treatment includes supportive individual and group psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy as needed to relieve the symptoms of anxiety, aggression and agitation typical of withdrawal and care. 21 days of hospitalization.	Drug: Oxytocin nasal spray; Oxytocin nasal spray 24 UI twice daily as adjunctive treatment to conventional treatment during 10 days of detoxification of crack cocaine
Placebo Comparator: Conventional treatment with placebo administration (T + PBO); 32 female cocaine users hospitalized for detoxification will receive six jets of placebo solution (2% odor-generating propolis essence + the same vehicle as intra-nasal oxytocin: 0.05% citric acid, 0.9% sodium chloride, 1% glycerol, 0.54% disodium phosphate, 0.2% methylparaben + propylparaben, 1% sorbitol, 80% water) twice daily as adjunctive treatment to conventional treatment from the eighth to the seventeenth day of hospitalization (duration of placebo treatment of 10 days). Conventional treatment includes supportive individual and group psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy as needed to relieve the symptoms of anxiety, aggression and agitation typical of withdrawal and care. 21 days of hospitalization.	Drug: placebo nasal spray; Nasal spray with placebo solution (2% odor-generating propolis essence + the same vehicle as intra-nasal oxytocin: 0.05% citric acid, 0.9% sodium chloride, 1% glycerol, 0.54% disodium phosphate, 0.2% methylparaben + propylparaben, 1% sorbitol, 80% water) twice daily as adjunctive treatment to conventional treatment.
No Intervention: Conventional treatment (T); 32 female cocaine users hospitalized for detoxification will receive conventional treatment including individual and group supportive psychotherapy (once a week), nutritional control, regular physical activity and psychopharmacotherapy if needed for symptom relief. anxiety, aggression and agitation, typical of abstinence and nursing care, during 21 days of hospitalization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Withdrawal symptoms	Change from baseline withdrawal symptoms (hospital admission) at the end of detoxification treatment (21 days) assessed by Cocaine Selective Severity Assessment (CSSA, minimum and maximum scores: 0 - 112). After treatment, the oxytocin-treated group is expected to have significantly lower withdrawal scores (better outcome) than the other groups (30%).	Change from baseline (first week after hospital admission) at the end of detoxification treatment (21 days).
Anxiety symptoms	Change from baseline anxiety symptoms (hospital admission) at the end of detoxification treatment (21 days) assessed by the Patient-Reported Outcomes Measurement Information System Short Form scale (PROMIS, minimum and maximum raw scores: 8 - 40). After treatment, the oxytocin-treated group is expected to show lower anxiety scores (better outcome) compared to the other groups (30%).	Change from baseline (first week after hospital admission) at the end of detoxification treatment (21 days).
Depression symptoms	Change from baseline depressive symptoms (hospital admission) at the end of detoxification treatment (21 days) assessed by the Quick Inventory of Depressive Symptomatology Self-Report scale (QIDS-SR, minimum and maximum scores: 0 - 27). After treatment, the oxytocin-treated group is expected to show lower depressive scores (better outcome) compared to the other groups (30%).	Change from baseline (first week after hospital admission) at the end of detoxification treatment (21 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroleptic Dose Change	Dose change of neuroleptic medications used during hospitalization for agitation or irritability (expected 25% lower).	Change from baseline (first week after hospital admission) at the end of detoxification treatment (21 days)
Adherence of outpatient treatment	Rate of adherence of outpatient treatment six months after discharge (expected to be 20% higher) assessed by reviewing the medical records of each patient within the outpatient program. If patient would be enrolled in the outpatient program after six months from detoxification she will be considered adhered to the program (higher rates means better outcome).	six months after hospital discharge

Collaborators and Investigators

• Sponsor: Pontificia Universidade Católica do Rio Grande do Sul
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico; Secretaria Nacional de Políticas sobre Drogas (SENAD)
• Investigators: Principal Investigator: Rodrigo Grassi-Oliveira, MD, PhD, Pontificia Universidade Católica do Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2018
• Primary Completion (Anticipated): April 30, 2020
• Study Completion (Anticipated): May 31, 2020

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: addiction; oxytocin; detoxification; withdrawal; crack cocaine; abstinence; stimulants
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: U1111-1188-6555 (Registry Identifier: Registro Brasileiro de Ensaios Clínicos); 39868314.0.0000.5336 (Registry Identifier: Plataforma Brasil)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: By the time of publication
• IPD Sharing Access Criteria: open access
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No