Use of Intranasal Oxytocin During Detoxification of Crack Cocaine

NCT04306354 | Completed Phase 1

• 2 other identifiers: U1111-1188-655539868314.0.0000.5336
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigated whether adding oxytocin nasal spray to usual inpatient treatment could reduce withdrawal, anxiety, and depressive symptoms in women hospitalized for cocaine detoxification. A total of 84 women were randomly assigned to one of three groups: usual treatment plus oxytocin nasal spray (30 participants), usual treatment plus placebo nasal spray (29 participants), or usual treatment alone (25 participants). Participants receiving a nasal spray and the staff administering it did not know whether it contained oxytocin or placebo. The usual-treatment-only group did not receive a nasal spray and was not masked. Symptoms were assessed during hospitalization, before, during, and after the intervention. Follow-up assessed relapse and duration of abstinence during the six months after discharge, using telephone contact with participants and family members and review of outpatient medical records. Outpatient treatment adherence was also a planned secondary outcome.

Conditions

Cocaine Withdrawal; Cocaine Smoking; Cocaine-Related Disorders

Keywords

crack cocaine; addiction; stimulants; oxytocin; detoxification; abstinence; withdrawal

Outcome Measures

Primary Outcomes (3)

• Change in Cocaine Withdrawal Symptoms

  Change from baseline to the end of inpatient detoxification in the Cocaine Selective Severity Assessment (CSSA) total score. Total scores range from 0 to 112, with higher scores indicating greater withdrawal symptom severity. Change is calculated as the end-of-treatment score minus the baseline score; negative values indicate improvement.

  Baseline (first week after hospital admission) and end of inpatient detoxification (up to hospital day 21).

• Change in Anxiety Symptoms

  Change from baseline to the end of inpatient detoxification in the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Short Form raw total score. Raw total scores range from 8 to 40, with higher scores indicating greater anxiety symptom severity. Change is calculated as the end-of-treatment score minus the baseline score; negative values indicate improvement.

  Baseline (first week after hospital admission) and end of inpatient detoxification (up to hospital day 21).

• Change in Depressive Symptoms

  Change from baseline to the end of inpatient detoxification in the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) total score. Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity. Change is calculated as the end-of-treatment score minus the baseline score; negative values indicate improvement.

  Baseline (first week after hospital admission) and end of inpatient detoxification (up to hospital day 21).

Secondary Outcomes (2)

• Neuroleptic Dose Change

  Change from baseline (first week after hospital admission) at the end of detoxification treatment (21 days)

• Percentage of Participants Enrolled in Outpatient Treatment at Six Months

  Six months after hospital discharge.

Study Arms (3)

Conventional Treatment Plus Intranasal Oxytocin (OXT)

EXPERIMENTAL

Participants received intranasal oxytocin in addition to conventional inpatient treatment. Each administration consisted of six sprays containing 4 IU each (24 IU per administration), given twice daily for a total daily dose of 48 IU. Treatment was administered from hospital day 8 through day 17, for 10 days. Conventional treatment included individual and group supportive psychotherapy, nutritional care, regular physical activity, nursing care, and psychopharmacotherapy as clinically indicated to manage withdrawal-related symptoms. The planned inpatient treatment period was 21 days.

Drug: Oxytocin nasal spray

Conventional Treatment Plus Intranasal Placebo (PBO)

PLACEBO COMPARATOR

Participants received intranasal placebo in addition to conventional inpatient treatment. Each administration consisted of six sprays of placebo solution, given twice daily from hospital day 8 through day 17, for 10 days. The placebo contained the same vehicle as the oxytocin formulation, with 2% propolis essence added for odor matching. Conventional treatment included individual and group supportive psychotherapy, nutritional care, regular physical activity, nursing care, and psychopharmacotherapy as clinically indicated to manage withdrawal-related symptoms. The planned inpatient treatment period was 21 days.

Drug: placebo nasal spray

Conventional Treatment Alone (CON)

ACTIVE COMPARATOR

Participants received conventional inpatient treatment alone, without intranasal oxytocin or placebo. Conventional treatment included individual and group supportive psychotherapy once weekly, nutritional care, regular physical activity, nursing care, and psychopharmacotherapy as clinically indicated to manage withdrawal-related symptoms, including anxiety, aggression, and agitation. The planned inpatient treatment period was 21 days.

Other: Conventional Inpatient Treatment

Interventions

Oxytocin nasal spray DRUG

Intranasal oxytocin was administered as six sprays containing 4 IU each (24 IU per administration), twice daily, for a total daily dose of 48 IU. Treatment was given from hospital day 8 through day 17, for 10 days, as an adjunct to conventional inpatient treatment.

Conventional Treatment Plus Intranasal Oxytocin (OXT)

placebo nasal spray DRUG

Intranasal placebo was administered as six sprays twice daily from hospital day 8 through day 17, for 10 days, as an adjunct to conventional inpatient treatment. The placebo contained the same vehicle as the oxytocin formulation, with 2% propolis essence added for odor matching.

Conventional Treatment Plus Intranasal Placebo (PBO)

Conventional Inpatient Treatment OTHER

Conventional inpatient treatment included individual and group supportive psychotherapy once weekly, nutritional care, regular physical activity, nursing care, and psychopharmacotherapy as clinically indicated to manage withdrawal-related symptoms, including anxiety, aggression, and agitation. The planned inpatient treatment period was 21 days.

Conventional Treatment Alone (CON)

Eligibility Criteria

• Age: 18 Years - 52 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female participants aged 18 to 52 years.
• Primary diagnosis of cocaine use disorder according to DSM-5 criteria. Other co-occurring substance use disorders were permitted, provided that cocaine was the primary drug of choice.
• Abstinence from cocaine for at least seven days before the intervention.
• Provision of informed consent and willingness to undergo random allocation to one of the study groups.

You may not qualify if:

• HIV-positive status.
• Pregnancy, postpartum status, or breastfeeding.
• Menopause.
• Current moderate or severe psychotic syndrome.
• Treatment with corticosteroids, synthetic glucocorticoids, or other exogenous hormone or steroid therapy.
• Intellectual impairment, defined as an intelligence quotient below 70.
• An infectious condition or acute febrile syndrome.
• Diagnosed or suspected neurological disease or syndrome, including current or previous stroke, epilepsy, cancer, or neurodegenerative disease.
• Diagnosed or suspected autoimmune disease or syndrome.
• Diagnosed or suspected current decompensated or severe cardiovascular, pulmonary, renal, gastrointestinal, or endocrine disease.
• History of moderate or severe traumatic brain injury, specified in the manuscript as a Glasgow Coma Scale score below 12.
• Significant nasal congestion preventing intranasal administration.
• Type III nasal septal deviation with impaired breathing.
• Nasal mucosal lesions.
• Class III obesity.

Sponsors & Collaborators

• Secretaria Nacional de Políticas sobre Drogas (SENAD): collaborator
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Pontificia Universidade Católica do Rio Grande do Sul: lead

Study Sites (1)

Hospital Santa Ana

Porto Alegre, Rio Grande do Sul, 91720-440, Brazil

Location

MeSH Terms

Conditions

Cocaine Smoking; Cocaine-Related Disorders; Behavior, Addictive

Condition Hierarchy (Ancestors)

Smoking, Non-Tobacco Products; Smoking; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior

Study Officials

• Rodrigo Grassi-Oliveira, MD, PhD

  Pontifícia Universidade Católica do Rio Grande do Sul

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants receiving intranasal treatment, personnel administering the nasal spray, and the investigator were blinded to oxytocin versus placebo assignment. The placebo contained the same vehicle as the oxytocin formulation, with propolis essence added for odor matching. Treatment assignments were unblinded at the end of the study by a postdoctoral researcher who was not otherwise involved in the project. The conventional-treatment-only group received no nasal spray and was not masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants were randomly allocated in a 1:1:1 ratio to three parallel groups: conventional inpatient treatment plus intranasal oxytocin, conventional inpatient treatment plus intranasal placebo, or conventional inpatient treatment alone. Randomization used blocks of 12 participants, with four assignments to each group, and was performed by a research team member who had no contact with participants.

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 12, 2020
• Study Start: September 17, 2018
• Primary Completion: January 12, 2020
• Study Completion: July 14, 2020
• Last Updated: September 28, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: De-identified individual participant data and analytic code will be available beginning six months after publication of the main study results and will remain available for five years.
• Access Criteria: Requests should be directed to the principal investigator and include a research proposal describing the objectives, requested data, and analysis plan. Access will be considered for scientifically sound proposals consistent with participant consent and applicable institutional and ethics requirements. Approved researchers will receive the de-identified data through a secure transfer mechanism after signing a data use agreement prohibiting participant re-identification and unauthorized redistribution.

Locations

BR (1)