Benzodiazepine DependencePhase 2NCT06757517
Effects of Intranasal Oxytocin in the Treatment of Benzodiazepine Withdrawal: A Pilot RCT
A Phase 2 study testing Oxytocin nasal spray in people with Benzodiazepine Dependence, run by St. Olavs Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Benzodiazepine Dependence
- What is being tested?
- Oxytocin nasal spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteNorway
- Study dates
- 1 Mar 2022to 29 Jan 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Intranasal Oxytocin in the Treatment of Benzodiazepine Withdrawal: A Pilot Randomized Parallel Group Placebo-Controlled Trial
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 questions 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?
Read more
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 nasal spray, three times daily for 21 days during inpatient benzodiazepine tapering.
Fill out an online questionnaire every day and keep a record of their symptoms.
Read the 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 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: Adults (aged 18-65) undergoing inpatient benzodiazepine tapering.
- Intervention: Participants were randomly assigned to receive either intranasal OT (16 IU per administration, given three times daily, for a total daily dose of 48 IU) or placebo for 21 days during inpatient benzodiazepine tapering.
- Assessments: Withdrawal symptoms were measured using the Clinical Institute Withdrawal Assessment for Benzodiazepines (CIWA-B) scale. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), and sleep was measured using the Insomnia Severity Index (ISI), actigraphy, and Somnofy.
Procedure
- Screening: Eligible participants underwent a screening process, including medical history, physical examination, and baseline assessments.
- Randomization: Participants were randomly assigned to the OT or placebo group.
- Treatment Phase: Participants self-administered the nasal spray three times daily for three weeks. Participants filled out daily questionnaires to monitor symptoms and side effects. Urine samples for toxicology were collected twice weekly during the intervention period, and blood samples were collected at screening and at the end of the intervention period.
- Post-Treatment Follow-Up: Participants were 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 was hypothesized that participants receiving intranasal OT would experience a significant reduction in withdrawal symptoms compared to the placebo group. Improvements in anxiety levels and sleep quality were 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
- Being tested
- Oxytocin nasal spray, Saline (NaCl 0,9 %) (placebo)
- Keywords
- intranasal oxytocin, oxytocin, benzodiazepines, benzodiazepine dependence, benzodiazepine withdrawal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxytocin nasal sprayDrug
Also called Syntocinon
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).
Saline (NaCl 0,9 %) (placebo)Drug
Saline intranasal placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Drug: Saline (NaCl 0,9 %) (placebo) |
| Oxytocin | Experimental | 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. Receives: Drug: Oxytocin nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Benzodiazepine withdrawal symptoms
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.
Measured: 21 days
Secondary outcomes (4)
Benzodiazepine craving
To test whether there is a difference between oxytocin and placebo on craving. Craving is measured daily with a Norwegian translation of the Brief Substance Craving Scale, adapted to benzodiazepines. Three items covering the intensity, frequency, and duration of craving during the past 24 hours are each scored from 0 to 4, giving a total score from 0 to 12. Higher scores indicate stronger craving, that is, a worse outcome. A fourth item records the number of craving episodes during the past 24 hours and is reported separately. The change in scores from baseline to day 21 is compared between the two study groups.
Measured: 21 days
Benzodiazepine anxiety and depression symptoms
To test whether there is a difference between oxytocin and placebo on rebound anxiety and depression symptoms. Symptoms are measured with the Hospital Anxiety and Depression Scale (HADS), a 14-item scale where each item is scored from 0 to 3, giving subscale scores from 0 to 21 for anxiety and for depression and a total score from 0 to 42. Higher scores indicate more severe symptoms, that is, a worse outcome. HADS is measured weekly from baseline to day 21, and the change in scores from baseline to day 21 is compared between the two groups.
Measured: 21 days
Benzodiazepine sleep distress
To test whether there is a difference between oxytocin and placebo on sleep. Sleep difficulties are measured with the Insomnia Severity Index (ISI), a 7-item scale where each item is scored from 0 to 4, giving a total score from 0 to 28. Higher scores indicate more severe insomnia, that is, a worse outcome. Sleep variables are also assessed by actigraphy and Somnofy. Scores are compared between the two study groups from baseline to day 21 during the intervention.
Measured: 21 days
Benzodiazepine tapering "freezes"
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.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2025
- Study start1 Mar 2022
- Primary completion6 Nov 2025
- Study completion29 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Benzodiazepine DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Olavs Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian University of Science and Technology, Lade Behandlingssenter, Blå Kors
- Responsible party
- Sponsor
- Investigators
- Tone Aurora Pleym, MD, PhD-candidate, Study chair, NTNU, Blue Cross, Clinic Lade, St. Olavs hospitalOlav Spigset, MD, PhD, Principal investigator, Department of Clinical Pharmacology, St. Olavs Hospital, and Norwegian University of Science and Technology (NTNU)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06757517
- Sponsor's protocol ID
- 32672
- Other IDs
- 2024-516262-11-00, 2019-002280-10, 2019
- Status last verified
- Sep 2026
- First submitted
- 17 Oct 2024
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No