Duloxetine Metabolism and Fibromyalgia

Recruiting

• Conditions: Fibromyalgia; Duloxetine
• Interventions: Drug: Observational

• Registration Number: NCT06866444
• Lead Sponsor: University of Utah

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.

Study Timeline

• Study First Submitted: 2025-03-04
• Study First Submitted QC: 2025-03-04
• Study First Posted: 2025-03-10
• Status Verified: 2025-05
• Study Start: 2025-05-01
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Primary Completion: 2026-05-01
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adult patients treated with duloxetine for fibromyalgia	Observational	Adults 18+ Meeting diagnostic criteria for Fibromyalgia Patients taking Duloxetine 60 mg/day for at least 8 weeks

Primary Outcome Measures

Name	Time	Method
Measure inhibitors and inducers of CYP1A2 and CYP2D6 in blood sample	Obtained four hours after the morning duloxetine dose.	Inhibitors and inducers of CYP1A2 and CYP2D6 are defined by the Drug Interaction Flockhart Table. A strong inhibitor will be measured by ≥ 5-fold increase in plasma AUC or more than 80% decrease in clearance. A moderate inhibitor will be measured by 2 to 5-fold increase in the plasma AUC or 50-80% decrease in clearance.
Duloxetine concentrations across metabolizer phenotypes, 3 groups	Obtained four hours after morning duloxetine dose.	Metabolizer phenotypes will be separated into 3 groups based on diplotypes. Ultrarapid metabolizer phenotypes will be measured by having an activity score of greater than 2.0. Normal/intermediate metabolizer phenotypes will be measured by having an activity score between 1.0 to 2.0. Slow metabolizer phenotypes will be measured by having an activity score between 0.75 to 0.

Secondary Outcome Measures

Name	Time	Method
Symptoms of fibromyalgia	From start of study visit to end (approximately 2 hours).	Measured by the Revised Fibromyalgia Impact Questionaire (FIQR) and ACR 2016 criteria for fibromyalgia. The FIQR is scored on a scale of 0-100, with higher scores (100) indicating a greater impact of fibromyalgia (worst outcome) and lower scores (0) indicating a lesser impact of fibromyalgia (better outcome).
Vital signs, noninvasive blood pressure	One time at the start of the study visit.	Blood pressure (mmHg) readings will be recorded.
Vital signs, oxygen hemoglobin saturation	One time at the start of the study visit.	Oxygen hemoglobin saturation (Sp02 using pulse oximeter) will be recorded.
Vital signs, temperature	One time at the start of the study visit.	Temperature (Celcius) will be recorded.
Vital signs, respiratory rate	One time at the start of the study visit.	Respiratory rate will be recorded (via observation for 1 minute).
Vital signs, heart rate	One time at the start of the study visit.	Heart rate (bpm) will be recorded.

Trial Locations

Locations (1)

Pain Management Center and Pain Research Center at the University of Utah; 🇺🇸 Salt Lake City, Utah, United States