Widespread Chronic PainPhase 3NCT02984397
Chronic Widespread Pain and White Blood Cell Activation
A Phase 3 study testing Ketotifen Fumarate in people with Widespread Chronic Pain, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 14 to 18 years
- Conditions the study is for
- Widespread Chronic Pain
- What is being tested?
- Ketotifen Fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2016to Jan 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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;
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- 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
Who cannot join
- 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;
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- 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 locations and contacts
1 site in 1 country.
Canada1 site
McGill University Health Centre (MUHC) - Montreal Children's Hospital
Montreal, Quebec, H4A 3J1
About this study
Official title: Proof of Concept Trial to Test the Efficacy of Treatment With Ketotifen on Pain Sensitivity and Association Between Level of Activity and Reactivity of White Blood Cells and Pain Sensitivity in Teenagers With Chronic Widespread Pain
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.
Read the detailed 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.
- Conditions
- Widespread Chronic Pain
- Being tested
- Ketotifen Fumarate, Placebo, Standard of Care
- Keywords
- pain, ketotifen, pediatric, mast cell
- Medical subject headings
- Chronic Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketotifen FumarateDrug
Also called Zaditen
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.
PlaceboDrug
Standard of CareOther
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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. Receives: 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 Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline versus week 16
Secondary outcomes (11)
Pain sensitivity
we will use a 0 to 10 numerical ranking scale adapted to RedCap to collect pain intensity ratings. In this scale, '0' means 'no pain at all' and '10' means 'the worst intense pain imaginable'. At baseline, weeks 4, 8, 12 and 16 clinical visits, patients will be asked by the research team to rate their lowest, average, and highest pain intensity for the previous day.
Intensity of the lowest, average, and highest pain at 'week 16' will be on of the secondary end points of the study.
Measured: Baseline versus week 16
Proportion of patients with pain sensitivity reduced by half
We are also interested in the proportion of patients that show a 50% reduction in their pain intensity after 16 weeks of treatment with KF. Thus, we will assess this proportion also for the lowest, average, and highest pain intensity.
Measured: Baseline versus week 16
Daily profile of pain index
As patients rate their lowest, average, and highest pain intensity daily on RedCap, they will be prompted to indicate also for how many hours each of these pains lasted. The product of pain intensity by pain duration (in hours) will generate the pain index (Example: pain intensity of 9 with a duration of 6 hours = pain index 54)
Measured: Across baseline and weeks 4, 8, 12 and 16 will be evaluated
Pressure pain sensitivity
Pressure pain thresholds (PPT) will be determined using a digital pressure algometer with a flat round transducer, applied bilaterally at the trapezius muscle and lateral epicondyle. Pressure will be increased at a steady rate of approximately 1 kg/s until the subject indicates that the pressure sensation is perceived as painful sensation (threshold), and the pressure in kg recorded. The first trial at each test site will be considered a practice trial, and will be excluded from data analysis. In subsequent trials, the pressure level at the time the subject indicates to first perceive the pressure sensation to become a painful sensation will be recorded as the threshold estimate. If no response is given at the point the algometer reaches maximum pressure, the maximum value will be used as the threshold value. This procedure will be repeated three times at each test site, and the mean value will be recorded as the subjects threshold.
Measured: Across baseline and weeks 4, 8, 12 and 16 will be evaluated
Functional Disability Inventory
The scale can be completed in person, by mail, or by phone. Scoring: item scores range from 0-4. The total FDI score is a sum of all of the items and can be easily hand scored. Scores range from 0-60, with higher scores indicating greater functional disability. (no/minimal disability 0 -12, moderate disability 13-29, and severe disability >30)
Measured: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Revised Child Anxiety and Depression Scale (RCADS)
): is a 47-item scale intended to assess children's report of symptoms corresponding to selected DSM-IV anxiety disorders and depression. The RCADS is a 47-item scale with subscales including: separation anxiety disorder (SAD), social phobia (SP), generalized anxiety disorder (GAD), panic disorder (PD), obsessive compulsive disorder (OCD), and major depressive disorder (MDD). It also yields a Total Anxiety Scale (sum of the 5 anxiety subscales) and a Total Internalizing Scale (sum of all 6 subscales). Recall period for item: one week. Scoring programs are available at www.childfirst.ucla.edu/resources for scoring the RCADS.
Measured: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Sleep
Pittsburgh Sleep Quality Index (PSQI): 19 items scale assessing sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. Recall period for item: one month Scoring: Point values of each item in of the seven subscales are summed and then combined as indicated to generate a subscale score. These totals are summed to create the global PSQI score.
Measured: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Role Functioning
Patients will be asked at each evaluation to quantify the number of days lost because of pain and/or associated symptoms in the previous four weeks. Days of school missed because of medical appointments will not be quantified for the role functioning analysis.
Measured: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Analgesic medication reduction
Patients will be allowed to reduce the doses or, eventually, to stop the use analgesic medication under medical supervision if there is a significant reduction in pain intensity (50% reduction in pain intensity rating) or in the associated symptoms
Measured: Compare baseline with weeks 4, 8, 12 and 16.
Adverse events
We will use an electronic list of adverse reactions to check for treatment-emergent adverse events. This list was created by us to run on RedCap, based on the list of adverse reactions reported by patients participating in a double-blind, placebo controlled Canadian Multicentre Trial (196 asthmatic children aged 5- 17 years) (Rackham, A. et al. A Canadian multicenter study with Zaditen (ketotifen) in the treatment of bronchial asthma in children aged 5 to 17 years. The Journal of allergy and clinical immunology 84, 286-296 (1989).
Measured: Compare weeks 4, 8, 12 and 16.
RNA expression
RNA expression patterns will be compared before and after treatment,
Measured: Baseline versus week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2016 (estimated)
- Study startDec 2016
- Primary completionJan 2020
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Widespread Chronic PainStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- The Louise And Alan Edwards Foundation
- Responsible party
- Principal investigator, Pablo Ingelmo, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02984397
- Sponsor's protocol ID
- 15-207-MUHC
- Status last verified
- Feb 2020
- First submitted
- 2 Dec 2016
- Last updated
- 20 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Trial to Test the Efficacy of Treatment With Ketotifen on Pain Sensitivity and Association Between Level of Activity and Reactivity of White Blood Cells and Pain Sensitivity in Teenagers With Chronic Widespread Pain
- ClinicalTrials.gov ID
- NCT02984397
- Acronym / sponsor ID
- 15-207-MUHC
- Conditions
- Widespread Chronic Pain
- Keywords
- pain, ketotifen, pediatric, mast cell
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Collaborators
- The Louise And Alan Edwards Foundation
- Study start
- Dec 2016 (actual)
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 6 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| KF group | Experimental | Drug: Ketotifen FumarateIn 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) |
| Placebo group | Placebo comparator | Drug: PlaceboPatients 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. |
| SOC | Active comparator | Other: Standard of CareStandard 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 |
Who may qualify
- Ages
- 14 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketotifen FumarateAlso: ZaditenKetotifen 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. | Drug | KF group |
| Placebo | Drug | Placebo group |
| Standard of Care | Other | SOC |
Primary outcome
Patients' Global Impression of Change (PGIC) scale
Time frame: Baseline versus week 16
"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.
11 secondary outcomes
Pain sensitivity
Time frame: Baseline versus week 16
Proportion of patients with pain sensitivity reduced by half
Time frame: Baseline versus week 16
Daily profile of pain index
Time frame: Across baseline and weeks 4, 8, 12 and 16 will be evaluated
Pressure pain sensitivity
Time frame: Across baseline and weeks 4, 8, 12 and 16 will be evaluated
Functional Disability Inventory
Time frame: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Revised Child Anxiety and Depression Scale (RCADS)
Time frame: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Sleep
Time frame: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Role Functioning
Time frame: Compare values at baseline, with those of weeks 4, 8, 12 and 16.
Analgesic medication reduction
Time frame: Compare baseline with weeks 4, 8, 12 and 16.
Adverse events
Time frame: Compare weeks 4, 8, 12 and 16.
RNA expression
Time frame: Baseline versus week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ketotifen Fumarate in people with Widespread Chronic Pain, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients' Global Impression of Change (PGIC) scale (time frame: Baseline versus week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020.