GoORT study. Version 1 25/08/2014
Research type
Research Study
Full title
Genetic influence on the success of opioid substitution therapy - role of variants of the cytochrome P450 enzyme family, and other genotypes, involved in methadone and buprenorphine metabolism. A pilot study to support the Fife Genetics of Opioid Replacement Therapy (GoORT) Bioresource
IRAS ID
158061
Contact name
Alexander Baldacchino
Contact email
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary
Methadone and buprenorphine substitute therapy is widely used to treat the withdrawal symptoms of opioid dependency in opioid dependent patients. The cytochrome P450 family of enzymes has a role in metabolising methadone/bupenorphine, reducing its availability in the body. Individuals may have different types of activity of several liver enzymes which break down this medicine quicker or slower than other patients, resulting in adverse clinical outcomes as a result of under or over medication. This breakdown usually happens through the cytochrome P450 enzyme family.
To investigae this, a sample of venous blood will be taken from consenting patients who currently access NHS Fife Addiction Services for the treatment of opioid dependency. Their cytochrome P450 genotype will be analysed using standard genotyping technology. Associations between genotypes, treatment dose and cessation of opioid use will be analysed.
We aim to identify areas where treatment for opioid dependency can be improved in patients by adjusting treatment to reflect their ability to effectively metabolise such opioids.Research Summary
The Go-ORT study was designed to investigate whether the success of methadone substitution therapy in opioid addicts, as assessed by stabilisation of patients on a low or high dose of methadone, depends on the person’s cytochrome P450, or CYP regulating nuclear receptor, genotype. The inter-individual variation in the metabolism, and therefore clinical efficacy, of methadone is predominantly due to genetic variation in the CYP genes coding for the various enzymes involved. These variations in metabolism may, unknowingly to the patient and the clinician, reduce predicted drug elimination rates through inhibition of drug metabolising enzymes or enhance drug elimination by increasing drug metabolising enzyme activity, with implications on therapeutic dosing and drug safety levels for patients’ methadone prescriptions. The study wanted to understand better whether the CYP genotype influenced the dose required to stabilise individuals on methadone substitution therapy.
During the recruitment period 136 participants were recruited out of an initial target of 500, a figure lower than initially proposed and probably a consequence of the negative effect of the COVID-19 pandemic on the research team workload, and limitations on patients being able to attend face-to-face clinics where recruitment activities would have been undertaken. DNA samples collected from the study participants underwent CYP genotype analysis and although we were able to identify whether an individual was a ‘poor’, ‘normal’, ‘intermediate’ or ‘ultra metaboliser’, there was not enough data collected during the study to make any statistically significant conclusions whether this impacted on the dose required to effectively treat opioid withdrawal symptoms in the patient group.REC name
West of Scotland REC 3
REC reference
14/WS/1123
Date of REC Opinion
8 Dec 2014
REC opinion
Further Information Favourable Opinion