Imperial College London
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ProfessorAnneLingford-Hughes

Faculty of Medicine, Department of Brain Sciences

Chair in Addiction Biology
 
 
 
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Contact

 

+44 (0)20 7594 8682anne.lingford-hughes Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Paterson:2022:10.1186/s13063-022-06821-9,
author = {Paterson, L and Lingford-Hughes, A and Cro, S and Phillips, R and Mozgunov, P and Paterson, S and Nahar, L and Barker, D and Smith, C},
doi = {10.1186/s13063-022-06821-9},
journal = {Trials},
title = {FORWARDS-1; An adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment; a pharmacokinetic-pharmacodynamic study},
url = {http://dx.doi.org/10.1186/s13063-022-06821-9},
volume = {23},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone.Methods:Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of ‘dose-limiting toxicity’ (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodicall
AU  - Paterson,L
AU  - Lingford-Hughes,A
AU  - Cro,S
AU  - Phillips,R
AU  - Mozgunov,P
AU  - Paterson,S
AU  - Nahar,L
AU  - Barker,D
AU  - Smith,C
DO  - 10.1186/s13063-022-06821-9
PY  - 2022///
SN  - 1745-6215
TI  - FORWARDS-1; An adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment; a pharmacokinetic-pharmacodynamic study
T2  - Trials
UR  - http://dx.doi.org/10.1186/s13063-022-06821-9
UR  - http://hdl.handle.net/10044/1/100389
VL  - 23
ER  -
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