Chronic Widespread Pain and White Blood Cell Activation

McGill University

Status and phase: Completed; Phase 3

Conditions: Widespread Chronic Pain

Treatments: Drug: Ketotifen Fumarate; Other: Standard of Care; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02984397

15-207-MUHC

Details and patient eligibility

About

Our goal is to conduct a proof-of-concept trial to test the efficacy of KF treatment in adolescents with severe CWP not responding to the standard of care (SOC) treatment program in a multidisciplinary tertiary care chronic pain clinic. The changes associated to the interventions (KF or placebo) will be quantified using the Patients' Global Impression of Change (PGIC) scale after 16 weeks of treatment. Secondary, we aim to evaluate the effects of KF on the pain sensitivity, physical and emotional functioning, and we will also explore the potential biological underlying mechanisms.

Full description

We have designed a proof-of-concept (POC) trial composed of three arms. The first two arms will be a randomized, controlled, double-blind, parallel-group study, designed to assess the potential efficacy of KF for the treatment of pain and associated symptoms in adolescent with CWP. The third arm will consists of assessing standard of care (SOC) data from patients who do not wish to participate in the study, but agree to allow us to use their SOC data to be compared with that of patients participating in the study. This arm will help to evaluate the potential beneficial effect of being part of the study ("placebo" effect) receiving a new treatment for a condition where the SOC have limited success rate.

Enrollment: 44 patients

Sex: All

Ages: 14 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female and male adolescents aged between 14 to 18 years old;
• For female adolescents of child bearing potential: negative serum pregnancy test at base line screening;
• For female adolescents of child bearing potential: being willing and able to use contraceptive methods for the duration of the study and for 30 days after receiving the last dose of the study drug;
• Diffuse body pain that has been present for at least 3 months, and who also have symptoms of fatigue, sleep disturbance, cognitive changes and mood disorder;
• Accompanied by at least one somatic symptoms to variable degree including irritable bowel syndrome, headaches, menstrual pain, lower urinary tract symptoms, myofascial pain, and temporomandibular pain;
• Symptoms cannot be explained by some other illness;
• Physical examination which should be within normal limits except for tenderness on pressure of soft tissues (i.e. tactile hyperalgesia which is increased pain following a painful stimulus)
• Overall body pain average score ≥ 4
• Moderate to severe physical impairment Functional Disability Inventory > 12 points.
• Stable doses of his/her current medication for at least four weeks
• Not having significant changes in their health conditions (PIGS less than 6 points) after 8 weeks of treatment

Exclusion criteria

• Be part of other trials;
• Have a specific diagnosis that can explain the symptoms; including rheumatoid arthritis, systemic lupus erythematosus, scleroderma and/or other connective tissue diseases
• Refuse to donate blood sample;
• Not be able to fill electronic records;
• Cognitive impairment interfering with the clinical evaluations;
• Known intolerance or allergies to KF;
• Been under treatment with other mast cell stabilizer agent;
• Seizures history or actual treatment;
• Coagulopathies or chronic thrombocytopenia;
• Atopic dermatitis (eczema) or chronic urticaria (hives)
• Schizophrenia or bipolar disorder
• Elective surgery within the study timeline
• Abnormal labs results (i.e., elevated SGPT and low platelet count, low Hb or Ht) in the last 6 months or in the base line evaluation
• Patients who are pregnant or are breast-feeding;
• Patients who are on oral antidiabetic agents;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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44 participants in 3 patient groups, including a placebo group

KF group

Experimental group

Description:

In each study visit, patients will receive enough pills for the next month. At the first visit, patients receiving ketotifen (KF) will receive four vials sequentially numbered (1 to 4) containing enough pills for one week each, and will be instructed by the clinician and by the pharmacist to use vial 1 for the first week (0.5 mg of KF BDI), vial 2 for the second week (1mg of KF BDI), vial 3 for the third week (2 mg of KF BDI), and vial 4 for the fourth week (3mg of KF BDI). As for weeks 4, 8 and 12 visits, patients treated with KF will receive four equal vials containing enough pills for one week each (3 mg of KF BDI)

Treatment:

Drug: Ketotifen Fumarate

Placebo group

Placebo Comparator group

Description:

Patients participating in the placebo group will also receive sequentially numbered vials at the first visit. Similarly, patients taking placebo will also receive four equal vials of pills on the next visits.

Treatment:

Drug: Placebo

SOC

Active Comparator group

Description:

Standard of care - patients who refuse to participate in the study but allow us to compare their clinical data to that of participants of the study

Treatment:

Other: Standard of Care