Fibromyalgia
Conditions
Keywords
Fibromyalgia
Brief summary
The objective of this protocol is to evaluate if Dextromethorphan (DXM) reduces Fibromyalgia (FM) pain. DXM is a drug found in several over-the-counter products, including cough suppressants. The drug may reduce FM pain by suppressing inflammation in the central nervous system. The investigators will be observing the effects of DXM on daily self-reported pain measures in people with FM. If DXM reduces FM pain, it will provide important information about the nature of FM pathophysiology.
Detailed description
Fibromyalgia (FM) is a chronic, widespread pain syndrome. Individuals with FM frequently report body pain, fatigue, sleep issues, cognitive impairment, headaches, and other symptoms. The disease affects approximately 5% of women in the United States. Many of those patients suffer with decreased quality of life and loss of employment. The precise pathological mechanism of FM is not yet understood, and there is no targeted treatment for the condition. One hypothesis of FM with prior scientific support is that pain is caused by abnormal inflammation of the brain. When microglia cells in the brain adopt an inflammatory state, they release chemicals that can cause neurons to increase the transmission of pain signals. DXM has been used in previous research and demonstrated to suppress pain symptoms. When given at higher dosages (above 200mg), the medication acts as a dissociative agent. This dosage can reduce pain, but produces side-effects that can limit daily functioning. At lower dosages, however, DXM may reduce inflammatory aspects of chronic pain while not causing dissociative side effects. In animal models, central inflammation can be reduced with intraperitoneal dosages of DXM of 0.1mg/kg. In an average U.S. woman, this dosage would translate to approximately 8mg. Because an oral versus intraperitoneal dosing route will be used, the dose will be raised to 10mg, administered twice a day (once in the morning and once at night). The investigator will examine the impact of 20mg total daily DXM on self-reported FM pain.
Interventions
DRUGDextromethorphan
(1)10 mg, by mouth, twice daily every 12 hours.
DRUGPlacebo
1 capsule, by mouth, twice daily every 12 hours.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
The participant will not know when they are taking placebo or the study medication.
Eligibility
Sex/Gender
FEMALE
Age
23 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Severe chronic fatigue ≥6 consecutive months not due to ongoing exertion or other medical condition associated with fatigue; 2. Daily self-reported pain of at least 4 out of 10; 3\. Meets American College of Rheumatology 2016 case definition criteria for FM; 4\. Able to attend UAB for all scheduled appointments; 5\. Can complete daily self-reports of pain and other symptoms for duration of project.
Exclusion criteria
1. Blood draw contraindicated or otherwise not able to be performed; 2. High-sensitivity C-reactive protein (HS-CRP) ≥ 10 mg/L; 3. Erythrocyte sedimentation rate (ESR) \>60 mm/hr; 4. Positive rheumatoid factor; 5. Positive anti-nuclear antibody (ANA); 6. Abnormal thyroid stimulating hormone or free thyroxine; 7. Diagnosed rheumatologic or auto-immune condition; 8. Blood or clotting disorder; 9. Use of blood thinning medication; 10. Current use of MAOI 11. Daily consumption of grapefruit juice 12. Oral temperature \>100˚F at baseline; 13. Febrile illness or use of antibiotics in the 4 weeks before study commencement; 14. Planned surgery or procedures during the study period, or operated on in the 4 weeks before study commencement; 15. Pregnant or planning on becoming pregnant within 6 months, or currently breastfeeding 16. Regular use of any anti-inflammatory medication (such as aspirin, ibuprofen, naproxen); 17. Baseline HADS (Hospital Anxiety and Depression Scale) depression subscale score of ≥16; 18. Current litigation or worker's compensation claim; 19. Current participation in another treatment trial; 20. Planned vaccination during the study period, or vaccinated in the 4 weeks before study commencement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Self-reported Pain Severity | Daily over 4 weeks | Daily self-reported widespread pain severity, rated on a 0 - 100 scale (0 = no pain and 100 = worst pain possible). Participants' daily scores from the last 4 weeks of each condition (placebo and dextromethorphan) were summed and then averaged across the 4-week time period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Self-reported Physical Activity | Daily over 4 weeks | Self-reported daily activity, rated from 0 - 100 where 0 is less daily activity and 100 is the most amount of daily activity. Participants' daily scores from the last 4 weeks of each condition (placebo and dextromethorphan) were summed and then averaged across the 4-week time period. |
| Patient Global Impression of Change | 20 weeks | Patient global impression of change (PGIC) measured on a seven point likert scale (1 = no change to 7 = a great deal better). PGIC's were not administered to participants. The PGIC was inadvertently left out of the lab visit packet. Since the PGIC was not administered, data was not collected for both arms/groups. |
Countries
United States
Participant flow
Pre-assignment details
27 participants attended the in-person screening visit and were enrolled into the study. Of the 27 enrolled, 19 met inclusion criteria and began the study protocol.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants first completed a 5-week placebo condition where they took one inert capsule in the morning, and one at night. They then completed a 10-week dextromethorphan condition where they took one 10 mg dextromethorphan capsule in the morning, and one at night. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Baseline Phase (2 Weeks) | Physician Decision | 1 |
| Dextromethorphan Phase (10 Weeks) | Withdrawal by Subject | 2 |
| Placebo Phase (5 Weeks) | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 47.07 years STANDARD_DEVIATION 10.74 |
| Duration of fibromyalgia illness | 10.19 years STANDARD_DEVIATION 6.9 |
| Fibromyalgia severity | 22.14 units on a scale STANDARD_DEVIATION 3.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 0 Participants |
| Symptom Severity Scale score | 8.36 units on a scale STANDARD_DEVIATION 2.1 |
| Widespread Pain Index score | 13.79 units on a scale STANDARD_DEVIATION 2.91 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 7 / 14 | 11 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
Daily Self-reported Pain Severity
Daily self-reported widespread pain severity, rated on a 0 - 100 scale (0 = no pain and 100 = worst pain possible). Participants' daily scores from the last 4 weeks of each condition (placebo and dextromethorphan) were summed and then averaged across the 4-week time period.
Time frame: Daily over 4 weeks
Population: All 14 participants underwent both the Dextromethorphan and Placebo conditions (within-subjects comparisons).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan | Daily Self-reported Pain Severity | 41.09 score/day | Standard Deviation 24.32 |
| Placebo | Daily Self-reported Pain Severity | 45.55 score/day | Standard Deviation 24.69 |
p-value: 0.146GEE
Secondary
Daily Self-reported Physical Activity
Self-reported daily activity, rated from 0 - 100 where 0 is less daily activity and 100 is the most amount of daily activity. Participants' daily scores from the last 4 weeks of each condition (placebo and dextromethorphan) were summed and then averaged across the 4-week time period.
Time frame: Daily over 4 weeks
Population: All 14 participants underwent both the Dextromethorphan and Placebo conditions (within-subjects comparisons).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan | Daily Self-reported Physical Activity | 46.92 score/day | Standard Deviation 19.79 |
| Placebo | Daily Self-reported Physical Activity | 50.10 score/day | Standard Deviation 19.7 |
p-value: 0.052GEE
Secondary
Patient Global Impression of Change
Patient global impression of change (PGIC) measured on a seven point likert scale (1 = no change to 7 = a great deal better). PGIC's were not administered to participants. The PGIC was inadvertently left out of the lab visit packet. Since the PGIC was not administered, data was not collected for both arms/groups.
Time frame: 20 weeks
Population: Scores for the PGIC secondary outcome were not available for analyses due to administrator error. PGIC's were not administered to participants. The PGIC was inadvertently left out of the lab visit packet. Since the PGIC was not administered, data was not collected for both arms/groups.