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

Study Overview
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Brief Summary
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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).

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

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo
* Drug: Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: • A simple randomization method will be used to assign the initial treatment and then the opposite treatment will ensure for the second treatment period. Patients will be randomized to (i) 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 or (ii) 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)<br>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)<br>* Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)<br>|
| Active Comparator: minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo<br>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<br>* minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Revised Fibromyalgia Impact Questionnaire (FIQR) score | change in subject reported difficulty experienced doing various tasks rate (no difficulty) to (very difficult) utilizing the Revised Fibromyalgia Impact Questionnaire (FIQR) score. | baseline and 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain, Enjoyment of Life and General Activity Scale (PEG) | Change in pain and interference (PEG) score based on the amount of interference pain has on a scale of 0(does not interfere)-10(completely interferes) in participant's average pain, enjoyment of life and general activity. | baseline and 20 weeks | 
| Patient Health Questionnaire (PHQ-2)54 | 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, several days, more than half the days or nearly everyday. | baseline and 20 weeks | 
| General Anxiety Disorder (GAD-2) | change in anxiety (GAD-2) scale by rating feelings of being nervous, anxious or on edge & not able to stop or control worrying. Participant rates feelings as not at all, several days, more than half the days or nearly everyday. | baseline and 20 weeks | 
| Patient Global Impression of Change (PGIC) | Change patient global impression of change (PGIC). The subject will report whether there was a change in 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) to much worse (10) | baseline and 20 weeks | 
| 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. | baseline and 20 weeks |