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NCT Number: NCT06757517

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

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.

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Key information

Conditions

Benzodiazepine Dependence

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Blue Cross, Clinic Lade

Trondheim, Trøndelag, 7091, Norway

Location status: Recruiting

Location contact

Tone Aurora Pleym MD, PhD-candidate

CONTACT

[email protected]

+47 97625583

About this study

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

  • Screening: Eligible participants will undergo a screening process, including medical history, physical examination, and baseline assessments.
  • Randomization: Participants will be randomly assigned to the OT or placebo group.
  • 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.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Oxytocin nasal spray

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).

Other names: Syntocinon

Saline (NaCl 0,9 %) (placebo)

Drug

Saline intranasal placebo comparator

Primary outcomes

  1. Benzodiazepine withdrawal symptoms

    Time frame: 21 days

    Benzodiazepine withdrawal symptoms severity is measured with CIWA-B score, a 20-item scale where each item can be assigned a score from 0 to 4, i.e. the total score can range from 0 and 80 points. CIWA-B score will be measured daily from baseline (i.e. the day before the intervention starts) to day 21.

Secondary outcomes

  1. Benzodiazepine craving

    Time frame: 21 days

    To test whether there is a difference between oxytocin and placebo on cravings. Comparing cravings scores measured daily with a 6-item Likert scale where the score can range between 0 to 5 points between the two study groups from baseline to day 21. Specifically, the change in scores from baseline to day 21 will compared between the two groups.

  2. Benzodiazepine anxiety and depression symptoms

    Time frame: 21 days

    To test whether there is a difference between oxytocin and placebo on rebound anxiety and depression symptoms. Comparing Hospital Anxiety and Depression rating scale (HAD) scores measuring psychological distress, anxiety and depression between the two study groups measured weekly from baseline to day 21. Specifically, the change in scores from baseline to day 21 will compared between the two groups.

  3. Benzodiazepine sleep distress

    Time frame: 21 days

    To test whether there is a difference between oxytocin and placebo on sleep. Comparing Insomnia Severity Index (ISI) scores measuring sleep difficulties, and sleep variables assessed by actigraphy and Somnofy, between the two study groups from baseline to day 21 during intervention.

  4. Benzodiazepine tapering "freezes"

    Time frame: 21 days

    To test whether there is a difference between oxytocin and placebo in the number of "freezes" in diazepam tapering. A "freeze" (not reducing the diazepam dose as scheduled during tapering) will be noted for each subject and compared between the two study groups.

Other outcomes

  1. Follow-up: Relapse

    Time frame: 15 weeks

    To test whether there is a difference between oxytocin and placebo in time to first benzodiazepine intake (up to 12 weeks after discharge). Comparing time (number of days) to first self-reported benzodiazepine intake after discharge (week 3) between the two study groups, by registration on the follow-up visits at week 7 and week 15.

  2. Follow-up: Benzodiazepine withdrawal symptoms

    Time frame: 15 weeks

    Difference between oxytocin and placebo group on withdrawal symptoms measured with CIWA-B at week 7 and week 15 after discharge.

  3. Follow-up: Benzodiazepine craving

    Time frame: 15 weeks

    To test whether there is a difference between oxytocin and placebo on cravings. Comparing cravings scores measured at week 7 and week 15 after discharge with a 6-item Likert scale where the score can range between 0 to 5 points between the two study groups from baseline to day 21.

  4. Follow-up: Benzodiazepine anxiety and depression symptoms

    Time frame: 15 weeks

    To test whether there is a difference between oxytocin and placebo on rebound anxiety and depression symptoms at week 7 and week 15 after discharge. Comparing Hospital Anxiety and Depression rating scale (HAD) scores measuring psychological distress, anxiety and depression between the two study groups.

  5. Follow-up: Benzodiazepine sleep distress

    Time frame: 15 weeks

    To test whether there is a difference between oxytocin and placebo on sleep distress at week 7 and week 15 after discharge. Comparing Insomnia Severity Index (ISI) scores measuring sleep difficulties.

Study contacts

Contact information is provided by the study sponsor or research team.

Olav Spigset MD, Professor of Clinical Pharmacology

CONTACT

[email protected]

+47 725 73 000

Tone Aurora Pleym, MD, PhD-candidate

CONTACT

[email protected]

+47 97 62 55 83

Sponsors and collaborators

Lead sponsor

St. Olavs Hospital

Other

Collaborators

  • Lade Behandlingssenter, Blå Kors
  • Norwegian University of Science and Technology

Registry information

Official study title

Effects of Intranasal Oxytocin in the Treatment of Benzodiazepine Withdrawal: A Pilot Randomized Parallell Group Placebo-Controlled Trial

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Jan 3, 2025
Registry last updated
Jan 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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