Fibromyalgia
Conditions
Keywords
Fibromyalgia, FMS
Brief summary
The purpose of this 10-week study is to determine the effects of a medication called Ketotifen on pain sensitivity; and fibromyalgia-related pain. Ketotifen works by inhibiting (to prevent or slow down) certain substances in the body that are known to cause inflammation. It is an antihistamine that reduces the harmful effects of histamine. The ophthalmic (eye drops) formulation of ketotifen has been approved by the Food and Drug Administration (FDA) and has been available in the United States for more than a decade. Oral (taken by mouth) ketotifen has been in available in other countries for several decades. Commonly prescribed for the maintenance treatment of asthma and allergic rhinitis, ketotifen has long track record of safety. To date, the oral form of ketotifen has not been approved by the FDA, therefore this study is referred to as an investigational drug study. Prior to opening recruitment an investigational new drug (IND) application which included scientific data and information regarding human safety plans was submitted to and approved by the FDA.
Detailed description
Approximately 46 subjects will be participating in this research. Each subject will be randomized (like flipping a coin) to one of two groups; approximately 23 volunteers will be randomized to receive the active medication and 23 will receive the placebo. Both groups will be blinded (will not know) to which group they have been assigned. The study will be conducted at the Indiana University Clinical Research Center for Pain (CRCP), located on the IUPUI campus in the National Institute of Fitness and Sport building,at 250 University Blvd.,Suite 118 Indianapolis, Indiana, 46202. To summarize: The subject will be asked to visit the CRCP on four separate occasions: Initial Screening, Week 1, Week 2, and Week 10. This study also includes, answering questionnaires, taking study medication, maintaining a written medication diary and agreeing to remain in weekly contact with the study team to answer a short side effect questionnaire. The side effect questionnaire will be conducted from week 1-4 and then once every 2 weeks from week 4-10. Study Overview: Week 0 (clinic visit 1): 1. Informed consent and initial screening questionnaire, 2. Review of all current medications 3. Light physical assessment, e.g. blood pressure, height, weight 4. The investigators will obtain a urine sample for a urine pregnancy test (UPT) 5. Complete short thumb pressure testing in order to set the testing parameters for futures tests (week 1 and week 10) 6. Receive 'pain score' wrist monitor with instructions to record his/her pain level three times each day for one week 7. Receive a one-week medication packet along with instructions to take one tablet twice a day for seven days along with entering dosing information in a medication diary. Week 1 (clinic visit 2): 1. Submit his/her pain score wrist monitor 2. Submit his/her medication diary for review and return any unused medication 3. Complete the self-assessment questionnaires via computer 4. Undergo a thumb pressures pain sensitivity test 5. If qualified to continue, the subject will receive the next 7-day supply of either a placebo or the active medication, ketotifen 1 mg. along with verbal and written instructions and a medication diary. Week 2 (visit 3): 1. The investigators will assess the subject's willingness to continue study participation. 2. Review medication diary and medication side-effect/benefit checklist along with any unused study medication. If the subject has not experienced any bothersome side effect and agree to continue,he/she will be issued the next level of either the placebo or the active medication Ketotifen (2 mg.). 3. To assure the subjects' safety, the project coordinator or a member of the research team will complete a medication side-effect questionnaire. The subject will be asked to schedule a weekly check-in call for week 3 and 4 and once every 2 weeks from week 4 to week 10 (weeks 6, 8, and 10) Week 10 (visit 4): 1. One week prior to this visit, the subject will receive a 'pain score' wrist monitor via an express delivery service (e.g., FedEx) and will be asked to enter his/her pain level three times a day for one week. Then return it during this visit. 2. Review medication side effect/benefit checklist, medication diary and return any unused medication. 3. Completion of self-assessment questionnaires via computer 4. Undergo a thumb pressures pain sensitivity test.
Interventions
DRUGKetotifen
After meeting the full eligibility requirement, participants will be randomized. From week 1 to 2, subjects will receive either ketotifen 1 mg by mouth, twice a day or the equivalent placebo. Thereafter, subjects will take ketotifen to 2 mg by mouth twice a day or the equivalent placebo.
After meeting the full eligibility requirement, participants will be randomized. From week 1 to 2, subjects will receive either ketotifen 1 mg BID or the equivalent placebo. Thereafter, subjects will take ketotifen to 2 mg BID or the equivalent placebo.
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
In order to qualify the subject: 1. must have been diagnosed with fibromyalgia by a medical doctor 2. must be between the ages of 18 to 65 years of age 3. must have a weekly overall body pain average score ≥ 4 4. must pass a screening questionnaire that calculates a physical impairment of ≥ 10 5. must be on stable doses of his/her current medication for at least past four weeks 6. must limit any changes in his/her medication(s) (e.g., dose change, addition or discontinuation of any medication that effects the central nervous system, e.g., benzodiazepines, sedative/hypnotic, etc. ) during the 10-week study period unless medically necessary 7. must report all medication including herbal supplements and over-the-counter medications, e.g. cold medication, eye drops, etc. that he/she is currently taking to a member of the research team 8. must be willing to maintain a medication diary provided to him/her during the 10-week study period 9. must be willing to abstain (not take) any fibromyalgia related medication including over-the-counter for at least 8-hours prior to each of the two testing visits (Otherwise, he/she may take these medication(s) immediately after pain sensitivity testing has been completed and as prescribed in-between visits) 10. must agree to use a proven method of contraception to prevent pregnancy throughout this study
Exclusion criteria
The subject will not be allowed to participate if: 1. he/she has a history of seizures 2. he/she has atopic dermatitis (also called eczema) or chronic urticaria (hives) 3. he/she has chronic thrombocytopenia (a low blood platelet count) 4. she is currently pregnant, are planning to become pregnant, or is breastfeeding 5. he/she has been diagnosed by a psychiatrist with Schizophrenia or bipolar disorder 6. he/she has been diagnosed with another major rheumatic conditions (i.e. rheumatoid arthritis, systemic lupus erythematosus, scleroderma and/or other connective tissue diseases) 7. he/she plans to undergo an elective surgery within the study timeline 8. he/she is in the process of filing, or plan to file for disability benefits within the study timeline 9. his/her screening labs results are abnormal (i.e., elevated SGPT and low platelet count) 10. he/she is currently using any anti-allergy drugs (ophthalmic or oral histamine antagonist), leukotriene inhibitors (e.g., montelukast) or prednisone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average Pain Score on the Visual Analog Scale at Week 10 | baseline and week 10 | Change in weekly average pain score from baseline to week 10 (range from -10 to +10): interpretation= the more negative the value is, the larger reduction in pain severity at week 10 is |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Evoked Pain Score at Week 10 | baseline and week 10 | Change in evoked pain score from baseline to week 10 (scale range -20 to +20): interpretation= the more negative the value is, the larger the reduction in sensitivity to pressure pain stimuli |
| Fibromyalgia Impact Questionnaire | baseline and week 10 | Change in global symptom severity \[scale range from -100 to +100\] = the more negative the value is, the greater the improvement in overall symptom severity |
| Change From Baseline in the Blood Levels of IL-8, MCP-1 and Eotaxin at Week 10 | baseline and week10 | Change in peripheral blood levels of IL-8, MCP-1 and Eotaxin from baseline to week 10 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketotifen Group Participants who received the active drug - ketotifen | 24 |
| Placebo Participants who received the placebo | 27 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 2 |
Baseline characteristics
| Characteristic | Ketotifen Group | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.1 years STANDARD_DEVIATION 8.5 | 51.3 years STANDARD_DEVIATION 8.5 | 51.2 years STANDARD_DEVIATION 8.4 |
| Evoked pain | 10.3 units on a scale STANDARD_DEVIATION 0.4 | 9.8 units on a scale STANDARD_DEVIATION 0.4 | 10.0 units on a scale STANDARD_DEVIATION 0.6 |
| Fibromyalgia impact questionnaire | 66.9 units on a scale STANDARD_DEVIATION 16.2 | 66.6 units on a scale STANDARD_DEVIATION 12 | 66.8 units on a scale STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 24 participants | 27 participants | 51 participants |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
| weekly average pain score | 6.5 units on a scale STANDARD_DEVIATION 0.9 | 6.2 units on a scale STANDARD_DEVIATION 1.3 | 6.4 units on a scale STANDARD_DEVIATION 1.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 24 | 1 / 27 |
| serious Total, serious adverse events | 6 / 24 | 1 / 27 |
Outcome results
Primary
Change From Baseline in Weekly Average Pain Score on the Visual Analog Scale at Week 10
Change in weekly average pain score from baseline to week 10 (range from -10 to +10): interpretation= the more negative the value is, the larger reduction in pain severity at week 10 is
Time frame: baseline and week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketotifen | Change From Baseline in Weekly Average Pain Score on the Visual Analog Scale at Week 10 | -1.33 units on a scale | Standard Deviation 1.92 |
| Placebo | Change From Baseline in Weekly Average Pain Score on the Visual Analog Scale at Week 10 | -1.54 units on a scale | Standard Deviation 1.93 |
Secondary
Change From Baseline in Evoked Pain Score at Week 10
Change in evoked pain score from baseline to week 10 (scale range -20 to +20): interpretation= the more negative the value is, the larger the reduction in sensitivity to pressure pain stimuli
Time frame: baseline and week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketotifen | Change From Baseline in Evoked Pain Score at Week 10 | -0.33 units on a scale | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Evoked Pain Score at Week 10 | -0.27 units on a scale | Standard Deviation 0.34 |
Secondary
Change From Baseline in the Blood Levels of IL-8, MCP-1 and Eotaxin at Week 10
Change in peripheral blood levels of IL-8, MCP-1 and Eotaxin from baseline to week 10
Time frame: baseline and week10
Population: We do not have data on the chemokines because of the problems we had with the assays. Indeed, IL-8, MCP-1 and Eotaxin were all secondary outcomes.
Secondary
Fibromyalgia Impact Questionnaire
Change in global symptom severity \[scale range from -100 to +100\] = the more negative the value is, the greater the improvement in overall symptom severity
Time frame: baseline and week 10
Population: Indeed, fibromyalgia impact questionnaire is a secondary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketotifen | Fibromyalgia Impact Questionnaire | -12.13 units on a scale | Standard Deviation 19.54 |
| Placebo | Fibromyalgia Impact Questionnaire | -12.27 units on a scale | Standard Deviation 18.12 |