The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia

The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia: a Double-blind, Randomized, Crossover Pilot Study

Evaluation of the effect of combinatorial treatment of fibromyalgia patients (standard of care + minocycline + N-acetylcysteine (NAC) relative to standard of care on subjective pain measurement Revised Fibromyalgia Impact Questionnaire (FIQR).

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily); Drug: minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Female
• Age 18 years or older
• Diagnosis of fibromyalgia for at least 6 months (confirmed by the modified 2010 ACR Diagnostic Criteria for Fibromyalgia Widespread Pain Inventory and Symptom Severity Scale)
• Currently on birth control or unable to become pregnant
• Willingness to avoid taking opioid and opiate medications during the duration of the study (5-6 months) Exclusion Criteria
• Known hypersensitivity to minocycline or tetracycline antibiotics or to N-acetylcysteine
• Current opioid therapy or planned initiation of opioid therapy
• Active pregnancy, lactation or plans to become pregnant in the next 6 months
• Significant hepatic disease as indicated by an AST or ALT greater than twice the upper limits of normal or bilirubin greater than twice the upper limits of normal
• Significant renal disease as indicated by an estimated glomerular filtration rate less than 60 mL/min/1.73m2 at baseline or during the first washout period
• History of autoimmune syndromes (systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis,
• History of intracranial hypertension or pseudotumor cerebri
• History of IBD (Crohns disease, ulcerative colitis), Clostridium difficile infection
• History of esophagitis, esophageal obstruction, achalasia or esophageal dysmotility
• History of GI hemorrhage or known risk factors for GI hemorrhage, such as esophageal varices, peptic ulcer disease, etc.
• Subjects taking divalent and trivalent cations such as oral iron supplements, certain dietary supplements (multivitamins) that contain manganese or zinc, or antacids that contain aluminum, calcium, or magnesium, which would decrease minocycline absorption
• Subjects taking anticoagulant medication since minocycline can decrease plasma prothrombin activity
• Subjects taking isotretinoin
• Subject taking ergot alkaloids for migraines
• Subjects taking penicillin antibiotics
• Subjects taking methoxyflurane containing products
• Subjects who work outdoors or otherwise have prolonged exposure to UV light and sunlight
• Lack of access to reliable technology to be able to complete emailed REDCap questionnaires
• Cognitive deficits that may make it difficult to adhere to the medication regimen or provide consistent and timely completion of questionnaires
• Inability or unwillingness to give informed consent
• Unwillingness to use two forms of birth control for the entire duration of participation in the study (if capable of becoming pregnant)
• Unwillingness to complete home pregnancy tests throughout the study (if capable of becoming pregnant)
• Inability to swallow large pills

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily); Participants will be randomized to 8 weeks of placebo, minimum 2 week washout period, and then 8 weeks of a combination minocycline (200 mg daily) and NAC (1200 mg daily) followed by a final 2 week washout	Drug: Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily); Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)
Active Comparator: minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo; Participants will be randomized to 8 weeks of a combination minocycline (200 mg daily) and NAC (1200 mg daily), minimum 2 week washout period, and then 8 weeks of placebo followed by a final 2 week washout	Drug: minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo; minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Revised Fibromyalgia Impact Questionnaire (FIQR) Score From Baseline to After Treatment Occurring at Weeks 8 and 18	The FIQR (Revised Fibromyalgia Impact Questionnaire) is comprised of 21 questions spread across 3 domains: function, overall impact, symptoms, scored on an 11-point numeric rating scale. The questions are framed with the context of the past 7 days. The instructions ask the patient to rate the difficulty on a scale of 0-10 (0 = No difficulty, and 10 = Very difficult) which indicates how much difficulty they have experienced in doing the specified activity during the past 7 days. Each item is rated on a scale from 0 - 10, and the raw scores on each subscale. Then, the score on the function subscale is divided by 3, the overall impact subscale divided by 1, and the symptoms subscale divided by 2. These final scores from each subscale are then added up for the total FIQR score The total score can range from 0 -100. The total FIQR score is the sum of each section. A lower score means a better outcome. Higher scores indicate more severe impact.	Evaluated at baseline (prior to intervention) then again after treatment which occurs at week 8 and week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain, Enjoyment of Life and General Activity (PEG) Scale From Baseline to After Treatment Occurring at Weeks 8 and 18	In the PEG score, a higher score indicates more severe pain and pain-related interference. The PEG has 3 separate numerical scales. Each has ratings 0-10.The first scale asks individuals to rate their pain, on average, over the past week, the second asks to rate how pain has interfered with their enjoyment of life in the past week, the third asks individuals to rate how pain has interfered with general activities. The PEG scale is scored by averaging the three numbers. The final score helps to track and monitor pain levels over time. The PEG score should decrease when treatment is effective.	Evaluated at baseline (prior to intervention) then again after treatment which occurs at week 8 and week 18
Change in Patient Health Questionnaire (PHQ-2) From Baseline to After Treatment Occurring at Weeks 8 and 18	The change in depression scale (PHQ-2) by evaluating the number of days the participant feels down, depressed or hopeless and has little interest or pleasure in doing things rated as not at all (0), several days (1), more than half the days (2), or nearly every day (3) by scoring the 2 questions from 0-3 as indicated. Scores range from 0-6, with the higher score meaning the patient experiencing more severe symptoms.	Evaluated at baseline (prior to intervention) then again after treatment which occurs at week 8 and week 18
Change in General Anxiety Disorder (GAD-2) Score From Baseline to After Treatment Occurring at Weeks 8 and 18	The Generalized Anxiety Disorder 2-item (GAD-2) screens for generalized anxiety disorder 1. Two questions are asked, with the scoring of each ranging from 0-3, then both numbers added together, with possible scores ranging from 0-6. A total score of at least 3 points indicates possible anxiety disorder. The higher the score, the more severe anxiety.	Evaluated at baseline (prior to intervention) then again after treatment which occurs at week 8 and week 18
Patient Global Impression of Change (PGIC)	Patient Global Impression of Change (PGIC) has the subject will reporting whether there was a change in their activity, limitations, symptoms, emotions and overall quality of life by rating "no change", "almost the same", "a little better", "somewhat better", "moderately better", "better" or "a great deal better". Participants will also rate degrees of change from much better (0), 5 (no change), to much worse (10). The higher the score, the worse their impression of their health status was worse than previously. Scores will range from no change to a great deal better, and from 0 (much better) to 10 (much worse).	immediately after each treatment at week 8 (first intervention) and week 18 (second intervention)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (Modified ACR 2010)	Participants will rate change using modified 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (modified ACR 2010) by answering questions related to their areas of pain, amount of medication required for pain, and symptoms.	Evaluated at baseline (prior to intervention) then again after treatment which occurs at week 8 and week 18

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Michael G Hillegass, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2021
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): August 31, 2022

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: 00102425

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No