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Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy (SMA)

This study is not yet open for participant recruitment.
Verified August 2017 by Hugh McMillan, Children's Hospital of Eastern Ontario
Sponsor:
ClinicalTrials.gov Identifier:
NCT02876094
First Posted: August 23, 2016
Last Update Posted: August 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Families of Spinal Muscular Atrophy
Gwendolyn Strong Foundation
Information provided by (Responsible Party):
Hugh McMillan, Children's Hospital of Eastern Ontario
  Purpose
Several factors make the use of celecoxib in human SMA patients appealing including: 1) low-dosing required for potential therapeutic effect (the corresponding dose in humans is much lower than that commonly used in adults and children with; 2) favourable side effect profile of this drug (particularly at the dosing required); 3) the fact that celecoxib crosses the blood brain barrier and 4) demonstration of efficacy in a genetically and pathophysiologically faithful animal mode. The investigators therefore believe that celecoxib is a promising disease modifying therapy for SMA.

Condition Intervention Phase
Spinal Muscular Atrophy (SMA) Drug: celecoxib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot, Open-Label, Dose Response Study Investigating the Effect of Low-Dose Celecoxib on SMN2 in Patients With Spinal Muscular Atrophy (SMA)

Resource links provided by NLM:


Further study details as provided by Hugh McMillan, Children's Hospital of Eastern Ontario:

Primary Outcome Measures:
  • low-dose oral celecoxib administered to patients with SMA type II and III is associated with an increase in the levels of peripheral leukocyte SMN protein compared to baseline [ Time Frame: baseline ]
    1) Investigate change in peripheral leukocyte SMN protein levels from baseline at each dose (40 mcg/kg, 80 mcg/kg, and 160 mcg/kg) of celecoxib.


Secondary Outcome Measures:
  • Safety Profile Measured by Adverse Event Frequency,Type and Severity [ Time Frame: 4 weeks post ]
    1) Determine safety profile as measured by number, type and severity of adverse events reported following administration of low dose celecoxib in patients with type II and III SMA

  • Recruitment Plan Measured by Number of Potentially Eligible Subjects [ Time Frame: 4 weeks post ]
    Assess understanding of recruitment barriers measured by the number of potentially eligible subjects and response to study recruitment phase.

  • Compliance Measured by Reported Protocol Deviations [ Time Frame: 4 weeks post ]
    Assess adherence to treatment protocol measured by number of reported protocol deviations.

  • Eligibility Measured by Number of Screen Failures [ Time Frame: 4 weeks post ]
    Assess appropriateness of eligibility criteria based on number of screen failures.

  • Delivery Time of Shipped Samples Assessed by Viability [ Time Frame: 4 weeks post ]
    Assess feasibility of shipping laboratory samples to outside centre for analysis. This will be reported based on the time to deliver and the resulting viability of the received samples by either pre or post testing or both if appropriate.


Estimated Enrollment: 12
Anticipated Study Start Date: August 2017
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-label
All patients will be treated at each dose of oral once daily celecoxib (40, 80 and 160 mcg/kg) for a period of two weeks, for a total of 6 weeks (42 days) of treatment.
Drug: celecoxib
dose-response
Other Name: CeleBREX

Detailed Description:
This is a pilot, open-label, dose-response study in patients with SMA type II or III. All patients will be treated at each dose of once daily celecoxib (40, 80 and 160 mcg/kg) for a period of two weeks, for a total of 6 weeks (42 days) of treatment.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed genetic diagnosis consistent with SMA that can include: SMN1 gene deletions, rearrangements and/or mutations
  2. Sufficient clinical information enabling the patient to be classified as either SMA type II or III. (Patients with SMA type II are defined as having achieved the motor milestone of sitting independently for > 30 seconds but not having been able to stand or walk unsupported. Patients with SMA type III are defined as having achieved the motor milestone of standing or walking independently).
  3. Confirmed genetic test result indicating number of SMN2 gene copies
  4. Age > 2.0 years old at screening
  5. Patients weighing at least 12 kg at screening
  6. Stable dosing (for at least 3 months) of medications that may affect function of muscle, nerve and/or neuromuscular transmission or gene expression (including but not limited to: coenzyme Q10, creatine monohydrate, nutritional supplements, oral salbutamol, valproic acid, sodium phenylbutyrate, hydroxyurea)
  7. Written informed consent obtained from patient and/or parents or legal guardians

Exclusion Criteria:

  1. Clinical presentation and/or genetic testing that is not consistent with SMA type II or III
  2. Inability or unwillingness to swallow celecoxib suspension
  3. Major surgery (scoliosis repair, G-tube insertion) within past 3 months
  4. Known hypersensitivity or allergy to celecoxib (including asthma, urticaria and/or other allergic symptoms resulting from prior celecoxib ingestion) or its excipients, or other NSAIDs (non-steroidal anti-inflammatory drugs) including ASA (Acetylsalicylic Acid)
  5. Known hypersensitivity or allergy to Ora-Blend® or its excipients
  6. Demonstrated allergic-type reaction to sulfonamides
  7. Celecoxib use within 2 weeks prior to screening visit
  8. Known cardiac (ie. uncontrolled heart failure, cerebrovascular bleeding, hypertension requiring the use of anti-hypertensive medication), hepatic (i.e. severe liver impairment or active liver disease), gastrointestinal (i.e. inflammatory bowel disease; active gastric/duodenal/peptic ulcer disease; or active gastrointestinal bleeding), hematologic (ie. thrombocytopenia defined as platelets < 50,000 or hemophilia), respiratory or renal disease(i.e. severe renal impairment defined as creatinine clearance < 30 mL/min) wherein the use of NSAIDs is contraindicated as per Product Monograph dated 03 March 2015.
  9. Concurrent use of medication contraindicated with Celecoxib use (including but not limited to, warfarin, fluconazole, lithium, hydrochlorothiazide)
  10. Female who is pregnant or breast feeding
  11. Female of child-bearing potential who is sexually active and unwilling or unable to use at least one form of highly effective and one effective method of birth control.
  12. Patients participating in any pharmaceutical clinical trial (with active agent) that could impact with the results of this study
  13. Inability or refusal to provide informed consent
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02876094


Contacts
Contact: Hugh McMillan, MD 613-737-7600 ext 1605 hmcmillan@cheo.on.ca
Contact: Angie Tuttle, BioTech,CCRP 613-737-7600 ext 6058 atuttle@cheo.on.ca

Locations
Canada, Ontario
Children's Hospital of Eastern Ontario Not yet recruiting
Ottawa, Ontario, Canada, K1H8L1
Contact: Hugh J McMillan, MD    613-737-7600 ext 1605    HMcMillan@cheo.on.ca   
Sponsors and Collaborators
Hugh McMillan
Families of Spinal Muscular Atrophy
Gwendolyn Strong Foundation
Investigators
Principal Investigator: Hugh McMillan, MD Children's Hospital of Eastern Ontario, Research Institute
  More Information

Responsible Party: Hugh McMillan, MD, MSc, FRCPC, FAAN, Pediatric Neurologist, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier: NCT02876094     History of Changes
Other Study ID Numbers: 15/22E
First Submitted: August 9, 2016
First Posted: August 23, 2016
Last Update Posted: August 2, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Results will be submitted for presentation at an international meeting and subsequently submitted for publication in a major international peer-reviewed medical journal.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents