Clinical trial NCT06866444: Duloxetine Metabolism and Fibromyalgia
Official title: Duloxetine Metabolism and Fibromyalgia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fibromyalgia
Duloxetine
Keywords: Duloxetine
Duloxetine metabolism
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2025-03-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated at the Pain Management Center (PMC) at the University of Utah who meet inclusion criteria.

Brief summary: 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.

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).

Primary outcomes:
measure: Duloxetine concentrations across metabolizer phenotypes, 3 groups
timeFrame: Obtained four hours after morning duloxetine dose.
measure: Measure inhibitors and inducers of CYP1A2 and CYP2D6 in blood sample
timeFrame: Obtained four hours after the morning duloxetine dose.
Secondary outcomes:
measure: Symptoms of fibromyalgia
timeFrame: From start of study visit to end (approximately 2 hours).
measure: Vital signs, heart rate
timeFrame: One time at the start of the study visit.
measure: Vital signs, noninvasive blood pressure
timeFrame: One time at the start of the study visit.
measure: Vital signs, oxygen hemoglobin saturation
timeFrame: One time at the start of the study visit.
measure: Vital signs, temperature
timeFrame: One time at the start of the study visit.
measure: Vital signs, respiratory rate
timeFrame: One time at the start of the study visit.
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Pain Management Center and Pain Research Center at the University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Jake Steenblick, DNP
role: PRINCIPAL_INVESTIGATOR
References: