To study the potential of baclofen as an anti-craving/relapse agent in GHB dependent patients.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Dependence and craving
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Substance use levels, as indexed by the total number of abstinent days, the
duration of continued abstinence after detoxification and level of substance
use over a period of 3 months (Timeline Followback).
Secondary outcome
These are:
- Craving levels, as indexed by self report using a visual analogue scale (VAS)
and the Desire for Drugs Questionnaire (DDQ) adapted to GHB.
- Psychiatric symptom levels (as indexed by self report Depression, Anxiety and
Stress Scale; DASS) and Quality of life (as measured with EQoL-5D).
Background summary
GHB dependence is a growing health problem in the Netherlands. Attempts to stop
using GHB are often followed by relapse in GHB use after successful
detoxification. Observations from the GHB monitor 1, show that craving and loss
of control symptoms, associated with GHB dependence, contribute to quick and
frequent relapse (two third of the patients within three months after
detoxification).
To date management of GHB dependence after detoxification consists mostly of
psychosocial treatment without pharmaco-therapeutic support. However, craving
for and loss of control over GHB use might also be relieved by
pharmaco-therapeutic treatment, as is the case in for example alcohol and
heroin dependence. GHB is a GABA-B receptor agonist. The addictive properties
of GHB are thought to be mediated by dopamine release in the mesolimbic
dopamine circuitry, as is the case in other addictive substances. Baclofen, a
muscle relaxant registered for the treatment of spasms and often prescribed
off-label for the treatment of narcolepsy, also acts as a GABA-B receptor
agonist. However, due to its specific receptor binding properties, it inhibits
dopamine release in the mesolimbic circuitry. This is thought to contribute to
its anti-craving properties and beneficial effects on relapse, as observed in
alcohol dependent patients. As such, baclofen might be particularly suitable in
the treatment of GHB dependence. Indeed, animal data have shown beneficial
effects of baclofen on GHB self-administration in mice and there is some
anecdotal evidence for beneficial effects on GHB withdrawal in humans.
The aim of the current study is to assess the potential of baclofen as an
anti-craving agent in GHB dependent patients. We hypothesize that
administration of baclofen to GHB dependent patients after detoxification is
associated with reduced levels of craving for and less frequent relapse in GHB
use, as compared to treatment as usual (without baclofen), without the
occurrence of serious adverse effects.
Study objective
To study the potential of baclofen as an anti-craving/relapse agent in GHB
dependent patients.
Study design
This study is designed as an open label clinical study with 100 GHB dependent
patients (between 18-65 years old) and is planned over the course of 24 weeks.
This study is a part of the National GHB Monitor 2.0. After successful
detoxification of GHB, patients will receive either treatment as usual, or
baclofen on top of treatment as usual, based on patient preference. Subjects
can only participate after written informed consent
Intervention
Patients will receive either baclofen as medication plus TAU or TAU alone.
Baclofen will be uploaded over a 2 week period to a maximum of 45-60 mg.
Baclofen will be administrated 3 times daily for 12 weeks.
Study burden and risks
In the current study participants are already taking part in the GHB monitor
2.0. This study protocol has already been approved by the medical ethical
board. In addition to the burden related to participation in that study,
participants of the current study will receive either TAU or TAU+ baclofen, as
to their preference. Monitoring of craving, substance use, psychiatric symptoms
and quality of life is part of the GHB monitor 2.0.
The additional burden of participating in this study on top of the
participation in the GHB monitor 2.0, consists mainly of the burden related to
baclofen administration, monitoring the effects of baclofen administration
(VAS, DDQ, calendar diary to track their medication consumption, relapse and
any side effects), and one extra follow-up measurement.
Based on previous studies using baclofen in the treatment of spasms and alcohol
dependence, the side effects are considered to be mild and transient, related
to a too rapid increase in dosage and mainly include: sleepiness and nausea.
In contrast with this burden, patients taking baclofen may benefit from
participation, given the expected positive effects on craving and substance
use, based on previous studies in both animals and humans using alcohol or GHB.
Piet Mondriaanlaan 50/52
Amersfoort 3812 GV
NL
Piet Mondriaanlaan 50/52
Amersfoort 3812 GV
NL
Listed location countries
Age
Inclusion criteria
GHB dependence is the primary diagnosis, according to the DSM-IV criteria. Patients are between 18-65 years old and should be able to read and speak Dutch sufficiently
Exclusion criteria
Patients with any current physical or psychiatric safety concerns are excluded. Exclusion criteria are:
- Presence of a somatic safety concerns. These include liver cirrhosis and impaired renal function (as indicated by aspartate aminotransferase (AST), alanine transaminase (ALT), or gamma-glutamyl transferase (GGT) level >3 times the upper limit of normal (ULN); bilirubin > ULN; serum creatinine > ULN) , unstable hypertension, diabetes mellitus, and seizure disorder, including well controlled cases, currently taking anticonvulsants, insulin, or oral hypoglycemic and pregnancy.
- History or presence of a current psychiatric disorder, including any mood disorder (bipolar disorder or major depressive disorder), any psychotic disorder (including schizophrenia), and/or suicidal ideations.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004170-94-NL |
| CCMO | NL40321.044.13 |