Dextromethorphan in Fibromyalgia

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.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Dextromethorphan; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama of Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dextromethorphan; Participant will take one dextromethorphan 10mg capsule in the morning and at night.	Drug: Dextromethorphan; (1)10 mg, by mouth, twice daily every 12 hours.
Placebo Comparator: Placebo; Participants will take one placebo capsule in the morning and at night.	Drug: Placebo; 1 capsule, by mouth, twice daily every 12 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Daily over 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Daily over 4 weeks
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.	20 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Jarred W Younger, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Actual): March 18, 2020
• Study Completion (Actual): March 18, 2020

Study Registration Dates

• First Submitted: January 19, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Fibromyalgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Respiratory System Agents; Antitussive Agents; Dextromethorphan
• Other Study ID Numbers: F161018005

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
• product manufactured in and exported from the U.S.: No