Duloxetine Metabolism and Fibromyalgia (Diligent)
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About
People with fibromyalgia report generalized body pain ("pain all over"), increased sensitivity to painful stimulation, chronic tiredness or low energy, sleep problems, and other physical and functional problems. The exact cause of the disorder is poorly understood, and treatment can be difficult.
The degree to which duloxetine is helpful for people with fibromyalgia varies greatly. For some people, it is very helpful for managing fibromyalgia symptoms. For others, people may not notice any benefit. Yet for some, it is a little helpful and the effect is noticeable only when people forget to take the medicine.
The purpose of this study is to collect data to better understand the relationship among gene types that control those enzymes, blood concentrations of duloxetine, and how it helps the symptoms.
Full description
Study Purpose: To study the variability of response in patients with fibromyalgia to treatment with duloxetine
Duloxetine is a common FDA-approved pharmacotherapy for fibromyalgia. However, there is significant treatment response variability. Prior work has explored the role of liver drug-metabolizing enzymes CYP2D6 and CYP1A2 in the biotransformation of duloxetine. The genes coding for these enzymes have many variants; some variants are rapid metabolizers, whereas others are slow metabolizers of duloxetine. The different variants may contribute to the wide range of treatment responses to duloxetine among fibromyalgia patients. Supporting duloxetine metabolism as a contributor to drug response variability, researchers have measured plasma duloxetine concentrations following recommended dosing regimens and found concentrations to have substantial variability.
A strong correlation between an ultra-rapid duloxetine metabolizer with a poor response to duloxetine will provide useful information when formulating a treatment plan. Patients with a poor response to duloxetine phenotype may be better served by another serotonin norepinephrine reuptake inhibitor such as milnacipran. Early identification of those who would benefit from duloxetine will help a personalized approach to treating fibromyalgia and optimize the cost-effectiveness of pharmacological interventions.
Drug interactions with duloxetine that influence drug effect: An important consideration in characterizing duloxetine metabolism is to account for drug interactions that may inhibit or induce CYP1A2 or CYP2D6.
The main objective of this proposal is to conduct a feasibility study/pilot study to serve as the basis for a larger study where we refine our study methodology. In a cohort of patients treated with duloxetine for fibromyalgia, this study will measure:
(i) Symptoms of fibromyalgia using a validated questionnaire.
(ii) Duloxetine plasma concentrations.
(iii) Genotype CYP2D6 and CYP1A2 and correlate their plasma concentrations and genotype (rapid, normal, or slow metabolizer) with fibromyalgia symptoms.
Hypotheses:
(i) Patients with rapid or slow metabolizing variants will have low and high duloxetine plasma concentrations respectively.
(ii) Patients with rapid metabolizing variants will have ineffective treatment with duloxetine and patients with slow metabolizing variants will have signs and symptoms of effective treatment or duloxetine toxicity.
(iii) Patients who consume inducers or inhibitors of CYP2D6 or CYP1A2 will have low and high duloxetine plasma concentrations, respectively. Patients who consume inducers of CYP2D6 or CYP1A2 will have ineffective treatment with duloxetine, and patients that consume inhibitors of CYP2D6 or CYP1A2 will have signs and symptoms of effective treatment or duloxetine toxicity.
Enrollment
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Inclusion criteria
- Adults 18+
- Meeting diagnostic criteria for Fibromyalgia
- Patients taking Duloxetine 60 mg/day for at least 8 weeks
Exclusion criteria
- Pregnant patients per verbal confirmation
- Patients that have a history of physician diagnosed kidney or liver disfunction or history of renal dialysis.
- Patients requiring an interpreter to communicate
- Patient's with progressive illnesses other than fibromyalgia that have a chronic pain and fatigue component (e.g., cancer patients receiving antineoplastic treatment, Parkinson's disease, Multiple Sclerosis).
Trial design
100 participants in 1 patient group
Trial contacts and locations
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Central trial contact
Natalie R Bennion, MPH; Ken B Johnson, MD
Data sourced from clinicaltrials.gov
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