Duloxetine Metabolism and Fibromyalgia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Observational.
- Who it may be relevant to
- Registry conditions: Fibromyalgia, Duloxetine. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Detailed 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.
Interventions
- Drug Observational
In a cohort of patients treated with duloxetine for fibromyalgia, participants vitals signs (blood pressure, heart rate, oxygen saturation level, temperature) will be taken as well as height and weight. Participants will fill out a questionnaire regarding their fibromyalgia diagnosis and symptoms. Lastly, participants will complete two sets of blood samples. One blood sample will evaluate genetic variants for duloxetine metabolizing capacity. The other sample will be used to analyze the level of
Primary outcome measures
- Duloxetine concentrations across metabolizer phenotypes, 3 groups [Time frame: Obtained four hours after morning duloxetine dose.]
- Measure inhibitors and inducers of CYP1A2 and CYP2D6 in blood sample [Time frame: Obtained four hours after the morning duloxetine dose.]
Secondary outcome measures (6)
- Symptoms of fibromyalgia [Time frame: From start of study visit to end (approximately 2 hours).]
- Vital signs, heart rate [Time frame: One time at the start of the study visit.]
- Vital signs, noninvasive blood pressure [Time frame: One time at the start of the study visit.]
- Vital signs, oxygen hemoglobin saturation [Time frame: One time at the start of the study visit.]
- Vital signs, temperature [Time frame: One time at the start of the study visit.]
- Vital signs, respiratory rate [Time frame: One time at the start of the study visit.]
Eligibility criteria
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).
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 1 center
- Pain Management Center and Pain Research Center at the University of Utah — Salt Lake City
Identifiers
NCT: NCT06866444 · IRB_00167537