The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia
Primary Purpose
Fibromyalgia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo
Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)
Sponsored by
About this trial
This is an interventional treatment trial for Fibromyalgia
Eligibility Criteria
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
Sites / Locations
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)
minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo
Arm Description
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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)
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.
Full Information
NCT ID
NCT04594733
First Posted
October 14, 2020
Last Updated
October 1, 2022
Sponsor
Medical University of South Carolina
1. Study Identification
Unique Protocol Identification Number
NCT04594733
Brief Title
The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia
Official Title
The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia: a Double-blind, Randomized, Crossover Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
December 6, 2021 (Actual)
Primary Completion Date
August 31, 2022 (Actual)
Study Completion Date
August 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of South Carolina
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibromyalgia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
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
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)
Arm Type
Active Comparator
Arm Description
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
Arm Title
minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo
Intervention Description
minocycline (200 mg daily) and NAC (1200 mg daily) followed by placebo
Intervention Type
Drug
Intervention Name(s)
Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)
Intervention Description
Placebo followed by minocycline (200 mg daily) and NAC (1200 mg daily)
Primary Outcome Measure Information:
Title
Revised Fibromyalgia Impact Questionnaire (FIQR) score
Description
change in subject reported difficulty experienced doing various tasks rate (no difficulty) to (very difficult) utilizing the Revised Fibromyalgia Impact Questionnaire (FIQR) score.
Time Frame
baseline and 20 weeks
Secondary Outcome Measure Information:
Title
Pain, Enjoyment of Life and General Activity Scale (PEG)
Description
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.
Time Frame
baseline and 20 weeks
Title
Patient Health Questionnaire (PHQ-2)54
Description
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.
Time Frame
baseline and 20 weeks
Title
General Anxiety Disorder (GAD-2)
Description
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.
Time Frame
baseline and 20 weeks
Title
Patient Global Impression of Change (PGIC)
Description
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)
Time Frame
baseline and 20 weeks
Title
modified 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (modified ACR 2010)
Description
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.
Time Frame
baseline and 20 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael G Hillegass, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Effect of Minocycline and N-acetylcysteine for the Treatment of Fibromyalgia
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