Clinical Trial Results:
ACUTE AND LONG-TERM EFFECTS OF INTRANASAL OXYTOCIN IN ALCOHOL WITHDRAWAL AND DEPENDENCE: A PROSPECTIVE RANDOMIZED PARALLEL GROUP PLACEBO-CONTROLLED TRIAL
Summary
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EudraCT number |
2015-004463-37 |
Trial protocol |
NO |
Global end of trial date |
30 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Dec 2021
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First version publication date |
13 Dec 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
140682
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02903251 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
St. Olavs University Hospital
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Sponsor organisation address |
St. Olavs hospital HF, Postboks 3250 Torgarden, Trondheim, Norway, 7006
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Public contact |
PI's representative(Katrine Melby), Lade Behandlingssenter, +47 92886639, katrine.melby@stolav.no
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Scientific contact |
PI's representative(Katrine Melby), Lade Behandlingssenter, 92886639 92886639, katrine.melby@stolav.no
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Sponsor organisation name |
St. Olavs University Hospital
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Sponsor organisation address |
Postboks 3250 Torgarden, Trondheim, Norway, 7006
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Public contact |
katrine.melby@stolav.no, Department of Clinical Pharmacology,
St. Olavs Universtiy Hospital, +47 92886639, katrine.melby@stolav.no
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Scientific contact |
katrine.melby@stolav.no, Department of Clinical Pharmacology,
St. Olavs Universtiy Hospital, +47 92886639, katrine.melby@stolav.no
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Oct 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Nov 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Nov 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary aim of the study is to test whether daily intranasal administration of oxytocin is more effective than placebo in decreasing the oxazepam dosages required to control withdrawal symptoms during a 3-day inpatient program of medical detoxification.
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Protection of trial subjects |
Treatment as usual, following the procedures for withdrawal symptoms of alcohol detoxification.
Reporting of adverse effects.
Clinical monitor.
Limiting number and duration of clinical tests in the detoxification period.
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Background therapy |
Benzodiazepin-treatment as usual, following the CIWA-Ar protocol at the detoxification ward. | ||
Evidence for comparator |
Oxytocin nasal spray alliviated alcohol withdrawal symptoms in a pilot trial. The main purpose of this study was to try to replicate the study and findings. | ||
Actual start date of recruitment |
01 Oct 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Norway: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
39
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 40 patients admitted for alcohol detoxification and withdrawal treatment at the Blue Cross Lade Addiction TreatmentCenter (LBS) in Trondheim, Norway. Eligible subjects were 18–65 years of age and lived in the county of Trøndelag, Norway. The inclusion period lasted from October 2016 to November 2017. | |||||||||
Pre-assignment
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Screening details |
Assessed for eligibility n = 138. Did not meet inclusion criteria (n = 96) Daily treatment with benzodiazepines or benzodiazepine-like hypnotics (n = 33) Negative alcohol breath test and > 15 h since last intake (n = 28) All other criteria (n= 55) Invited to participate (n = 42). Declined to participate (n = 2) | |||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Oxytocin | |||||||||
Arm description |
Subjects were given six insufflations of the nasal spray (containing a total dose of 24 IU oxytocin or placebo) in interchanging nostrils with 15 s in between insufflations, twice daily for 3 days. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Syntocinon
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Investigational medicinal product code |
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Other name |
Oxytocin
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Intranasal use
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Dosage and administration details |
Subjects were given six insufflations of the nasal spray (containing a total dose of 24 IU oxytocin or placebo) in interchanging nostrils with 15 s in between insufflations. x 2 daily for 3 days.
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Arm title
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Placebo | |||||||||
Arm description |
subjects were given six insufflations of the placebo nasal spray (containing placebo) in interchanging nostrils with 15 s in between insufflations twice daily for 3 days. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo spray containing the same constituents as Syntocinon, except oxytocin.
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Intranasal use
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Dosage and administration details |
subjects were given six insufflations of the placebo nasal spray (containing placebo) in interchanging nostrils with 15 s in between insufflations twice daily for 3 days.
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Baseline characteristics reporting groups
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Reporting group title |
Oxytocin
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Reporting group description |
Subjects were given six insufflations of the nasal spray (containing a total dose of 24 IU oxytocin or placebo) in interchanging nostrils with 15 s in between insufflations, twice daily for 3 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
subjects were given six insufflations of the placebo nasal spray (containing placebo) in interchanging nostrils with 15 s in between insufflations twice daily for 3 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Oxytocin
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Reporting group description |
Subjects were given six insufflations of the nasal spray (containing a total dose of 24 IU oxytocin or placebo) in interchanging nostrils with 15 s in between insufflations, twice daily for 3 days. | ||
Reporting group title |
Placebo
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Reporting group description |
subjects were given six insufflations of the placebo nasal spray (containing placebo) in interchanging nostrils with 15 s in between insufflations twice daily for 3 days. |
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End point title |
Total oxazepam dosage in milligrams | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
3 days of detoxification.
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Statistical analysis title |
Total oxazepam dose | ||||||||||||
Comparison groups |
Placebo v Oxytocin
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.49 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-22.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-86.9 | ||||||||||||
upper limit |
42.4 |
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End point title |
CIWA-ar | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
3 days
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Statistical analysis title |
CIWA-Ar score | ||||||||||||
Comparison groups |
Oxytocin v Placebo
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.665 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.54
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.03 | ||||||||||||
upper limit |
1.95 | ||||||||||||
Variability estimate |
Standard deviation
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End point title |
HSCL-10 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
3 days
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Statistical analysis title |
HSCL-10 | ||||||||||||
Comparison groups |
Placebo v Oxytocin
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.945 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.15
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-4.38 | ||||||||||||
upper limit |
4.09 | ||||||||||||
Variability estimate |
Standard deviation
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End point title |
Self-reported sleep | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
3 days
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Statistical analysis title |
Self-reported sleep | ||||||||||||
Comparison groups |
Oxytocin v Placebo
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.535 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.64
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-2.72 | ||||||||||||
upper limit |
1.44 | ||||||||||||
Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
3 days
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Assessment type |
Systematic | ||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Oxytocin
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Reporting group description |
- | ||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Large variability in mg oxazepam. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/30784955 http://www.ncbi.nlm.nih.gov/pubmed/32053696 http://www.ncbi.nlm.nih.gov/pubmed/33352584 |