Chronic Widespread Pain and White Blood Cell Activation

NCT02984397 | Completed Phase 3

• 1 other identifier: 15-207-MUHC
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Widespread Chronic Pain

Keywords

pain; ketotifen; pediatric; mast cell

Outcome Measures

Primary Outcomes (1)

• Patients' Global Impression of Change (PGIC) scale

  "Since beginning treatment, how would you describe the change (if any) in ACTIVITY LIMITATIONS, SYMPTOMS, EMOTIONS and OVERALL QUALITY OF LIFE related to your painful condition?" (CHOOSE ONE). * No change (or condition has got worse) * Almost the same, hardly any change at all * A little better, but not noticeable change at all * Somewhat better, but the change has not made any real difference * Moderately better, and a slight but noticeable change * Better, and a definite improvement that has made a real and worthwhile difference * A great deal better, and a considerable improvement that has made all the difference Patients scoring either 6 or 7 on the PGIC scale are categorized as "improved". Patients scoring either 6 or 7 on the PGIC scale are categorized as "improved". We will use this definition as a dichotomous variable.

  Baseline versus week 16

Secondary Outcomes (11)

• Pain sensitivity

  Baseline versus week 16

• Proportion of patients with pain sensitivity reduced by half

  Baseline versus week 16

• Daily profile of pain index

  Across baseline and weeks 4, 8, 12 and 16 will be evaluated

• Pressure pain sensitivity

  Across baseline and weeks 4, 8, 12 and 16 will be evaluated

• Functional Disability Inventory

  Compare values at baseline, with those of weeks 4, 8, 12 and 16.

Study Arms (3)

KF group

EXPERIMENTAL

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)

Drug: Ketotifen Fumarate

Placebo group

PLACEBO COMPARATOR

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.

Drug: Placebo

SOC

ACTIVE COMPARATOR

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

Other: Standard of Care

Interventions

Ketotifen Fumarate DRUG

Ketotifen is a second-generation noncompetitive H1-antihistamine and mast cell stabilizer. It is most commonly sold as a salt with fumaric acid, ketotifen fumarate, and is available in two forms. In its ophthalmic form, it is used to treat allergic conjunctivitis, or the itchy red eyes caused by allergies. In its oral form, it is used to prevent asthma attacks.

Also known as: Zaditen

KF group

Placebo DRUG

Placebo group

Standard of Care OTHER

SOC

Eligibility Criteria

• Age: 14 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• The Louise And Alan Edwards Foundation: collaborator

Study Sites (1)

McGill University Health Centre (MUHC) - Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

MeSH Terms

Conditions

Chronic Pain; Pain

Interventions

Ketotifen; Standard of Care

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Anesthesia; Director, Chronic Pain Service (Pediatric), Montreal Children's Hospital

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 6, 2016
• Study Start: December 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: February 20, 2020

Record last verified: 2020-02

Locations

CA (1)