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

NCT02878798 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: URNN001 / HM200140831U01NS095388
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 20

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

Outcome Measures

Primary Outcomes (2)

• Intraepidermal Nerve Fiber Density (IENFD)

  Difference in IENFD change between treatment groups over 96 weeks (fibers/mm) (i.e. the slope of change). A skin biopsy is obtained. The sample is stained for nerve fibers. The rate of change in IENFD in fibers/mm is calculated over the 96 week duration of the study and expressed in change in fibers/mm/year (defined as 52 weeks) over the study period (i.e. the slope of change expressed and change in IENFD in fibers/mm over a 52 week period).

  96 weeks

• Norfolk Quality of Life - Diabetic Neuropathy

  Difference in NQOL between treatment groups over 96 weeks. The Norfolk QOL-DN is a validated 47-item, patient-reported outcome measure, sensitive to the different features of diabetic neuropathy (DN) including small fiber, large fiber, and autonomic function. A lower score is better. The range of the score is from -4 to 136. The slope of the change in total Norfolk QOL-DD is calculated as the change in total score/52 weeks (one year)

  96 weeks (expressed as a slope in change of total score/52 weeks)

Secondary Outcomes (10)

• Brief Pain Inventory - Diabetic Neuropathy (BPI-DN) Pain Interference

  96 weeks (expressed as a change in change in pain interference/52weeks)

• Brief Pain Inventory - Diabetic Neuropathy (BPI-DN) Average Pain Intensity

  96 weeks (expressed as a slope of change over 52 weeks)

• Utah Early Neuropathy Scale

  96 weeks (expressed as a slope of change in total UENS over 52 weeks).

• Sural Sensory Amplitude (SSA)

  96 weeks (slope of change in mV/52weeks)

• Peroneal Motor Conduction Velocity (PMCV)

  96 weeks (expressed as a slope of change in meter/sec over 52 weeks)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Topiramate

EXPERIMENTAL

Oral topiramate

Drug: topiramate

Interventions

topiramate DRUG

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

Also known as: Topamax

Topiramate

Placebo OTHER

overencapsulated placebo of identical color, shape and packaging to topiramate

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80
• 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.
• Evidence of symptomatic neuropathy based on a screening visit NQOL-DN score of \>9.
• 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% .
• No current or prior history of therapy with topiramate.
• 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.
• 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.

You may not qualify if:

• 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.
• Type I diabetes or current use of insulin or use of insulin in the past 3 months.
• HgA1c \> 7.5%. Borderline screening labs can be repeated within two weeks with PPI approval.
• History of recurrent nephrolithiasis, a single episode of nephrolithiasis within one year prior to screening, or use of ongoing preventative treatment.
• Family history of a hereditary neuropathy in a first-degree relative.
• Severe neuropathy: Utah Early Neuropathy Score \> 24 at screening
• Active foot ulceration or a history of a nontraumatic foot amputation.
• ECG with QTc more than 450 ms in men, or 470 ms in women.
• Risk of excessive bleeding at the skin biopsy site based on the clinical assessment of the CSS-PI.
• Chronic corticosteroid use excluding topical or inhaled treatment.
• Use of a carbonic anhydrase inhibitor (such as acetazolamide) due to risk of nephrolithiasis.
• Planned bariatric surgery.
• Use of other weight loss medications.
• Use of scheduled opiates, or as needed opiate medications more than three times weekly.
• Use of topical capsaicin products within 16 weeks of screening or at any time on study.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• NeuroNEXT Network: collaborator

Study Sites (20)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Neurology Clinical Trials Organization

Ann Arbor, Michigan, 48105-2945, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Eastern Virginia Medical Center

Norfolk, Virginia, 23510, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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.

  PMID: 37870862 DERIVED

MeSH Terms

Interventions

Topiramate

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Dr. A. Gordon Smith
• Organization: Virginia Commonwealth University

gordon.smith@vcuhealth.org

801-828-9869

Study Officials

• Gordon Smith, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2016
• First Posted: August 25, 2016
• Study Start: February 12, 2018
• Primary Completion: September 28, 2021
• Study Completion: September 28, 2021
• Last Updated: November 14, 2023
• Results First Posted: November 14, 2023

Record last verified: 2023-10

Locations

US (20)