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

NCT ID: NCT02878798

Last Updated: 2023-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-12
• Study Completion Date: 2021-09-28

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.

Conditions

Cryptogenic Sensory Peripheral Neuropathy in Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

An overencapsulated placebo of identical color, shape and packaging to topiramate will be used.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

overencapsulated placebo of identical color, shape and packaging to topiramate

Topiramate

Oral topiramate

Group Type: EXPERIMENTAL

topiramate

Intervention Type: DRUG

Oral topiramate at a target dose of 50mg twice daily.

Interventions

topiramate

Oral topiramate at a target dose of 50mg twice daily.

Intervention Type: DRUG

Placebo

overencapsulated placebo of identical color, shape and packaging to topiramate

Intervention Type: OTHER

Other Intervention Names

Topamax

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

NeuroNEXT Network

OTHER

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gordon Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

University of Alabama Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

University of California Irvine

Orange, California, United States

University of Miami

Miami, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Neurology Clinical Trials Organization

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

UT Southwestern Medical Center

Dallas, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Eastern Virginia Medical Center

Norfolk, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

Smith AG, Singleton JR, Aperghis A, Coffey CS, Creigh P, Cudkowicz M, Conwit R, Ecklund D, Fedler JK, Gudjonsdottir A, Hauer P, Herrmann DN, Kearney M, Kissel J, Klingner E, Quick A, Revere C, Stino A; NeuroNEXT NN108 TopCSPN Study Team. Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome: The TopCSPN Randomized Clinical Trial. JAMA Neurol. 2023 Dec 1;80(12):1334-1343. doi: 10.1001/jamaneurol.2023.3711.

Reference Type: DERIVED

PMID: 37870862 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1U01NS095388

Identifier Type: NIH

Identifier Source: secondary_id

View Link

URNN001 / HM20014083

Identifier Type: -

Identifier Source: org_study_id