E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benzodiazepine withdrawal and craving |
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E.1.1.1 | Medical condition in easily understood language |
Benzodiazepine withdrawal and craving |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033329 |
E.1.2 | Term | Oxytocin |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary aim of the study is to test whether there is a difference between daily intranasal administration of oxytocin or placebo for 21 days added to a dose reduction regime of diazepam in 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. Change in CIWA-B from baseline to day 21 will compared between the two groups. |
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E.2.2 | Secondary objectives of the trial |
The secondary aims are to test whether there is a difference between oxytocin and placebo on cravings (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), on rebound anxiety and depression symptoms (comparing HAD scores measured weekly from baseline to day 21), on sleep (assessed by actigraphy and Somnofy), number of "freezes" in diazepam tapering (number of times not reducing the diazepam dosage as scheduled). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients aged 18 – 65 years, taking BZDs at a daily dose of 20-80 mg diazepam-equivalent, and requiring inpatient BZD withdrawal. Included patients must consent to participate in the study. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is measuring BZD withdrawal symptoms to see if OT administered intranasally in addition to traditional dose tapering is more effective than BZD tapering and placebo. The Clinical Institute Withdrawal Assessment Scale for Benzodiazepines (CIWA-B) is a well-known and well-used 20-item questionnaire for BZD withdrawal symptoms where each item can be assigned a score from 0 to 4, i.e. the total score can range between 0 points and 80 points. Three items are considered objective measurements in which they are reviewed by health personnel. Few previous studies have been conducted with the use of the CIWA-B scale. What score can be considered of clinical interest is therefore based upon the results from previous studies using CIWA-B as a measurement for benzodiazepine withdrawal symptoms, and our clinical experience. Based on this we have chosen to consider a 3.5-point difference to be clinically relevant. The questionnaire is previously translated to Norwegian and is considered standard, generally reliable and relevant to the objective set forth. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the 4 week inpatient stay (day 21 of intervention period). |
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E.5.2 | Secondary end point(s) |
Hamilton Anxiety and Depression Scale (HAD), Insomnia Severity Index (ISI) and actigraphy and Somnofy assessed akathisia and sleep. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completed 4 weeks inpatient stay (day 21 of intervention period). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |