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Topiramate for Cryptogenic Sensory Peripheral Neuropathy in Metabolic Syndrome (CSPN) (TopCSPN)

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ClinicalTrials.gov Identifier: NCT02878798
Recruitment Status : Recruiting
First Posted : August 25, 2016
Last Update Posted : June 4, 2019
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
NeuroNEXT Network
Information provided by (Responsible Party):
Virginia Commonwealth University

Tracking Information
First Submitted Date  ICMJE August 11, 2016
First Posted Date  ICMJE August 25, 2016
Last Update Posted Date June 4, 2019
Actual Study Start Date  ICMJE February 12, 2018
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Intraepidermal nerve fiber density (IENFD) [ Time Frame: Baseline 9, 18, and 24 months ]
    Difference in IENFD change between treatment groups over 24 months.
  • Norfolk Quality of Life - Diabetic Neuropathy [ Time Frame: Screening, 4, 8, 12, 16, 20, and 24 months ]
    Difference in NQOL between treatment groups over 24 months.
Original Primary Outcome Measures  ICMJE
 (submitted: August 21, 2016)
  • Intraepidermal nerve fiber density (IENFD) [ Time Frame: Baseline 9, 18, and 24 months ]
    Difference in IENFD change between treatment groups over 24 months.
  • Norfolk Quality of Life - Diabetic Neuropathy [ Time Frame: Baseline, 9, 18, and 24 months ]
    Difference in NQOL between treatment groups over 24 months.
Change History Complete list of historical versions of study NCT02878798 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Nerve conduction studies [ Time Frame: Baseline, 8, 16, and 24 months ]
    Association of NCS outcomes to NQOL and IENFD changes
  • Utah Early Neuropathy Scale [ Time Frame: Screening, 4, 8, 12, 16, 20, 24 months ]
    association of UENS to NQOL and IENFD changes
  • Timed up and Go [ Time Frame: Baseline, 8, 16, and 24 months ]
    association of TUG change to NQOL and IENFD changes
  • 6 Minute Walk Test [ Time Frame: Baseline, 8, 16, and 24 months ]
    association of 6MW change to NQOL and IENFD changes
  • Neuropathy Total Symptom Score - 6 [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
  • Brief pain inventory [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
    association of BPI change to NQOL and IENFD changes
Original Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2016)
  • Nerve conduction studies [ Time Frame: Baseline, 9, 18, and 24 months ]
    Association of NCS outcomes to NQOL and IENFD changes
  • Utah Early Neuropathy Scale [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
    association of UENS to NQOL and IENFD changes
  • Timed up and Go [ Time Frame: Baseline, 9, 18 and 24 months ]
    association of TUG change to NQOL and IENFD changes
  • 6 Minute Walk Test [ Time Frame: Baseline, 9, 18, and 24 months ]
    association of 6MW change to NQOL and IENFD changes
  • Neuropathy Total Symptom Score - 6 [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
  • Berg Balance Test [ Time Frame: Baseline, 9, 18, and 24 months ]
    association of BBT change to NQOL and IENFD changes
  • Visual analog pain scale [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
    association of VAS change to NQOL and IENFD changes
  • Brief pain inventory [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
    association of BPI change to NQOL and IENFD changes
  • Mini-Best Test [ Time Frame: Baseline, 4, 8, 12, 16, 20, 24 months ]
    association of MBT change to NQOL and IENFD changes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Topiramate for Cryptogenic Sensory Peripheral Neuropathy in Metabolic Syndrome (CSPN)
Official Title  ICMJE Topiramate as a Disease Modifying Therapy for Cryptogenic Sensory Peripheral Neuropathy in Metabolic Syndrome (CSPN)
Brief Summary The TopCSPN trial is a double blinded randomized placebo controlled study of oral topiramate as a potential disease modifying therapy for cryptogenic sensory peripheral neuropathy (CSPN). Patients with CSPN who also have metabolic syndrome (defined by the ATPIII criteria) who do not have an alternative cause for neuropathy will be potentially eligible. The co primary outcome measures are change in the Norfolk Quality of Life - Diabetic Neuropathy (NQOL-DN) Scale and intraepidermal nerve fiber density (IEFND) at the distal thigh. The treatment phase will last 24 months.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cryptogenic Sensory Peripheral Neuropathy in Metabolic Syndrome
Intervention  ICMJE
  • Drug: topiramate
    Oral topiramate at a target dose of 50mg twice daily.
    Other Name: Topamax
  • Other: Placebo
    overencapsulated placebo of identical color, shape and packaging to topiramate
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    An overencapsulated placebo of identical color, shape and packaging to topiramate will be used.
    Intervention: Other: Placebo
  • Experimental: Topiramate
    Oral topiramate
    Intervention: Drug: topiramate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 21, 2016)
125
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Age 18-80
  2. Diagnosis of confirmed symptomatic distal symmetric peripheral polyneuropathy based on the Toronto consensus criteria for probable neuropathy (the presence of unequivocal signs and symptoms of neuropathy)45.
  3. Evidence of symptomatic neuropathy based on a screening visit NQOL-DN score of >9.
  4. Metabolic syndrome based on modified ATPIII criteria. Specific criteria require 3 of the following 6 to be present at the screening visit.

    • Waist circumference >102 cm for men, >88 cm for women
    • Serum triglycerides of > 150 mg/dl
    • HDL < 40 mg/dl for men, < 50 mg/dl for women
    • Those with either a normal HDL or TRG who are taking a lipid lowering medication for this purpose
    • Blood pressure 130/85 mm Hg or use of anti-hypertension drug
    • Hyperglycemia based on American Diabetes Association (ADA) criteria at screening based on any one or more of the following: fasting plasma glucose > 100 mg/dL (5.6 mmol/L), 2-hour glucose tolerance test > 140 mg/dL (7.8 mmol/L), or hemoglobin A1c > 5.7% .
  5. No current or prior history of therapy with topiramate.
  6. If female of child-bearing potential (i.e., not surgically sterile or post-menopausal defined as age > 51 years without menses for ≥ 2 years), negative serum pregnancy test at screening and negative urine pregnancy test at baseline visit.
  7. Women of child-bearing potential or men with sexual partners of childbearing potential be willing to use an acceptable method of birth control for the duration of the study and for 12 weeks following completion of study drug therapy. Acceptable methods of birth control include abstinence, oral contraceptives, the contraceptive patch, intra-uterine device, the contraceptive ring, and or barrier contraception such as condoms with spermicide.

Exclusion Criteria

  1. CSS-PI clinical determination of an alternative cause for peripheral neuropathy (including but not limited to rheumatological disorders, Hepatitis B or C, breast cancer treated with neurotoxic chemotherapy within the past 15 years). All potential subjects will have screening neuropathy labs including assessment for diabetes (Hemoglobin A1c, oral glucose tolerance test), vitamin B12 level, and immunofixation47.
  2. Type I diabetes or current use of insulin or use of insulin in the past 3 months.
  3. HgA1c > 7.5%. Borderline screening labs can be repeated within two weeks with PPI approval.
  4. History of recurrent nephrolithiasis, a single episode of nephrolithiasis within one year prior to screening, or use of ongoing preventative treatment.
  5. Family history of a hereditary neuropathy in a first-degree relative.
  6. Severe neuropathy: Utah Early Neuropathy Score > 24 at screening
  7. Active foot ulceration or a history of a nontraumatic foot amputation.
  8. ECG with QTc more than 450 ms in men, or 470 ms in women.
  9. Risk of excessive bleeding at the skin biopsy site based on the clinical assessment of the CSS-PI.
  10. Chronic corticosteroid use excluding topical or inhaled treatment.
  11. Use of a carbonic anhydrase inhibitor (such as acetazolamide) due to risk of nephrolithiasis.
  12. Planned bariatric surgery.
  13. Use of other weight loss medications.
  14. Use of scheduled opiates, or as needed opiate medications more than three times weekly.
  15. Use of topical capsaicin products within 16 weeks of screening or at any time on study.
  16. Medication change for neuropathy symptoms during the 8 weeks prior to screening; or anticipated change for the duration of study participation.
  17. Current use of an intrathecal pain pump or spinal cord stimulator.
  18. Screening laboratory creatinine ≥ 2.0 mg/dl.
  19. Severe edema, dermatologic or lower extremity condition that would increase risk of skin biopsy.
  20. Major depression, bipolar affective disorder, or other mental health disorders that are sufficiently severe to increase adverse event risk or impact neuropathy assessment in the opinion of the responsible site principal investigator.
  21. Current suicidal ideation within one year prior to the baseline visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS).
  22. Ataxia sufficiently severe to represent an unacceptable fall risk in the opinion of the site principal investigator.
  23. A serious medical condition expected to dramatically shorten life span or prevent participation.
  24. Any clinically significant condition or illness, which, in the opinion of the CSS-PI, would pose a risk to the subject or might confound the study including metabolic acidosis, bone marrow suppression, blood dyscrasias, bleeding disorder, or closed angle glaucoma.
  25. History of alcohol or drug abuse within the past two years, or existing neuropathy related to past drug or alcohol abuse.
  26. History of malignancy within five years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  27. A history of epilepsy.
  28. An inability to understand or cooperate with the procedures of the study.
  29. Pregnant, or intending to become pregnant, or breastfeeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gordon Smith, MD 804-828-9556 gordon.smith@vcuhealth.org
Contact: Brittney A Holmberg 804-552-0014 brittney.holmberg@vcuhealth.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02878798
Other Study ID Numbers  ICMJE URNN001 / HM20014083
1U01NS095388 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Virginia Commonwealth University
Study Sponsor  ICMJE Virginia Commonwealth University
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • NeuroNEXT Network
Investigators  ICMJE
Principal Investigator: Gordon Smith, MD Virginia Commonwealth University
PRS Account Virginia Commonwealth University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP