Effects of Intranasal Oxytocin in the Treatment of Benzodiazepine Withdrawal: A Pilot RCT

NCT ID: NCT06757517

Last Updated: 2025-01-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2025-12-31

Brief Summary

The goal of this clinical trial is to learn if oxytocin administered as a nasal spray will reduce withdrawal symptoms in adults during benzodiazepine tapering for 21 days. It will also learn about the safety of oxytocin. The main question it aims to answer are:

Does oxytocin reduce benzodiazepine withdrawal symptoms and make it easier to succeed tapering? Does oxytocin help reduce sleep difficulties and anxiety or restlessness during benzodiazepine tapering? Does oxytocin help reduce benzodiazepine craving?

We will compare oxytocin nasal spray to a placebo nasal spray containing regular saline to see if oxytocin works accordingly.

Participants will:

Take oxytocin or a placebo nasalspray, thrice daily for 21 days during inpatient benzodiazepine tapering.

Fill out an online questionnaire every day and keep a record of their symptoms.

Detailed Description

Background Benzodiazepine withdrawal can be challenging, often accompanied by severe anxiety, insomnia, and other withdrawal symptoms. Recent studies suggest that intranasal oxytocin (OT) may have anxiolytic properties and could potentially ease withdrawal symptoms. This pilot study aims to evaluate the efficacy and safety of intranasal OT in the treatment of benzodiazepine withdrawal.

Objectives The primary objective is to evaluate if intranasal OT can reduce withdrawal symptoms in patients during benzodiazepine tapering. Secondary objectives include evaluating the safety and tolerability of intranasal OT and its impact on anxiety levels and sleep quality.

Methods

• Design: This is a randomized, parallel-group, placebo-controlled trial.
• Participants: 60 adults (aged 18-65) who are undergoing benzodiazepine tapering.
• Intervention: Participants will be randomly assigned to receive either intranasal OT (24 IU) or a placebo, administered twice daily for four weeks.
• Assessments: Withdrawal symptoms will be measured using the Clinical Institute Withdrawal Assessment for Benzodiazepines (CIWA-B) scale. Anxiety levels will be assessed using the Hamilton Anxiety Rating Scale (HAM-A), and sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI) and actigraphy recordings.

Procedure

1. Screening: Eligible participants will undergo a screening process, including medical history, physical examination, and baseline assessments.

2. Randomization: Participants will be randomly assigned to the OT or placebo group.

3. Treatment Phase: Participants will self-administer the nasal spray thrice daily for three weeks. Participants will fill out daily questionnaires to monitor symptoms and side effects. Weekly urine- and blood samples will be collected.

4. Post-Treatment Follow-Up: Participants will be assessed at the end of the treatment period and again four and twelve weeks post-treatment to evaluate the persistence of effects.

Expected Outcomes It is hypothesized that participants receiving intranasal OT will experience a significant reduction in withdrawal symptoms compared to the placebo group. Improvements in anxiety levels and sleep quality are also anticipated.

Significance This study could provide preliminary evidence for the use of intranasal OT as a supportive treatment for benzodiazepine withdrawal, potentially improving patient outcomes and comfort during the tapering process.

Conditions

Benzodiazepine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants in the placebo arm will receive a saline solution. Saline is an inert substance, meaning it has no therapeutic effect, making it an ideal placebo. The saline solution will be administered in the same manner as the experimental treatment. The treatment is administered intranasally. The treatment is blinded. Neither the participants nor the researchers know who is receiving the placebo and who is receiving the active treatment. Participants in the placebo arm will be monitored the same as those in the treatment arm. Participants will be fully informed about the possibility of receiving a placebo and will provide informed consent. The same outcome measures will be used for both the placebo and treatment arms.

Group Type: PLACEBO_COMPARATOR

Saline (NaCl 0,9 %) (placebo)

Intervention Type: DRUG

Saline intranasal placebo comparator

Oxytocin

Participants in this arm will receive intranasal oxytocin. The dosage and administration schedule will be consistent with the study protocol. Participants will receive 48 international units (IU) of oxytocin. The oxytocin will be administered intranasally using a nasal spray. Participants will insert the nasal spray container approximately 1 cm into each nostril and spray. They will wait 15 seconds before repeating administration until they have received a total of 4 puffs (2 in each nostril) per session thrice daily.

Group Type: EXPERIMENTAL

Oxytocin nasal spray

Intervention Type: DRUG

Syntocinon contains synthetic oxytocinfor intranasal use, 6.7 microg (4 IU) per dose. We are planning to use 4 insufflations (16 IU) three times daily (i.e. a total daily dose of 48 IU).

Interventions

Oxytocin nasal spray

Syntocinon contains synthetic oxytocinfor intranasal use, 6.7 microg (4 IU) per dose. We are planning to use 4 insufflations (16 IU) three times daily (i.e. a total daily dose of 48 IU).

Intervention Type: DRUG

Saline (NaCl 0,9 %) (placebo)

Saline intranasal placebo comparator

Intervention Type: DRUG

Other Intervention Names

Syntocinon

Eligibility Criteria

Inclusion Criteria

• Patients aged 18 - 65 years, taking benzodiazepines at a daily dose of 20-80 mg diazepam-equivalent, and requiring inpatient benzodiazepine withdrawal. Included patients must consent to participate in the study.

Exclusion Criteria

• Female patients will be excluded if they are pregnant or are planning to become so, or if they are breast-feeding. Individuals incapable of completing questionnaires or giving informed consent will be excluded. Patients with concurrent acute medical or psychiatric illness requiring acute care hospitalization, misuse or dependency of alcohol or pregabalin/gabapentin will be excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Norwegian University of Science and Technology

OTHER

Sponsor Role: collaborator

Lade Behandlingssenter, Blå Kors

UNKNOWN

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tone Aurora Pleym, MD, PhD-candidate

Role: STUDY_CHAIR

NTNU, Blue Cross, Clinic Lade, St. Olavs hospital

Locations

Blue Cross, Clinic Lade

Trondheim, Trøndelag, Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Tone Aurora Pleym, MD, PhD-candidate

Role: CONTACT

tone.pleym@ntnu.no

+47 97 62 55 83

Olav Spigset MD, Professor of Clinical Pharmacology

Role: CONTACT

olav.spigset@legemidler.no

+47 725 73 000

Facility Contacts

Tone Aurora Pleym MD, PhD-candidate

Role: primary

tone.pleym@ntnu.no

+47 97625583

Other Identifiers

32672

Identifier Type: -

Identifier Source: org_study_id