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

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ClinicalTrials.gov Identifier: NCT02876094
Recruitment Status : Terminated (Terminated: Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention)
First Posted : August 23, 2016
Last Update Posted : October 19, 2020
Families of Spinal Muscular Atrophy
Gwendolyn Strong Foundation
Information provided by (Responsible Party):
Hugh McMillan, Children's Hospital of Eastern Ontario

Brief Summary:
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 or disease Intervention/treatment Phase
Spinal Muscular Atrophy (SMA) Drug: celecoxib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
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)
Actual Study Start Date : January 29, 2019
Actual Primary Completion Date : August 6, 2020
Actual Study Completion Date : August 6, 2020

Arm Intervention/treatment
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
Other Name: CeleBREX

Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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.

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

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

  5. 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.

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

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

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

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Canada, Ontario
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H8L1
Sponsors and Collaborators
Hugh McMillan
Families of Spinal Muscular Atrophy
Gwendolyn Strong Foundation
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Principal Investigator: Hugh McMillan, MD Children's Hospital of Eastern Ontario Research Institute
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Responsible Party: Hugh McMillan, MD, MSc, FRCPC, FAAN, Pediatric Neurologist, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier: NCT02876094    
Other Study ID Numbers: 15/22E
First Posted: August 23, 2016    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action