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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
132
Oral topiramate at a target dose of 50mg twice daily.
overencapsulated placebo of identical color, shape and packaging to topiramate
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
...and 10 more locations
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).
Time frame: 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)
Time frame: 96 weeks (expressed as a slope in change of total score/52 weeks)
Brief Pain Inventory - Diabetic Neuropathy (BPI-DN) Pain Interference
Pain interference score. Each item is scored from 0-10 with a total possible number of points of 70, higher worse. The range of the score is 0-70. The change in score is expressed as a slope of change in pain interference score/52 weeks (one year)
Time frame: 96 weeks (expressed as a change in change in pain interference/52weeks)
Brief Pain Inventory - Diabetic Neuropathy (BPI-DN) Average Pain Intensity
Average pain severity. Each item is scored 0-10 with a total of 40 possible points, higher is worse. The range of the score is 0-40. The slope of the change in this score is expressed as change/one year (defined as 52 weeks)
Time frame: 96 weeks (expressed as a slope of change over 52 weeks)
Utah Early Neuropathy Scale
The UENS is a validated examination score of neuropathy severity based on a physical examination (Singleton et al 2008). Total score is 42 (minimum 0 and maximum 42). The higher the score, the worse the outcome is. The change in UENS over the 96 week period is expressed as a slope of change in total UENS over one year defined as 52 weeks.
Time frame: 96 weeks (expressed as a slope of change in total UENS over 52 weeks).
Sural Sensory Amplitude (SSA)
Change in SSA measured in microvolts. SSA is measured by electrically stimulating a nerve through the skin and recording the response. A larger value is better. The normal values vary based on age, with a minimum of 0 (absent). Across all ages, the lower limit of normal is 6 microvolts, although the normal cutoff declines with aging. The change in SSA over the 96 week study period is expressed as a slope of change in uV/52 weeks (the 52 week log (mV) change of non-zero values).
Time frame: 96 weeks (slope of change in mV/52weeks)
Peroneal Motor Conduction Velocity (PMCV)
PMCV change. PMCV is measured by electrically stimulating the nerve through the skin at two different locations and measuring how fast the response travels between the two in meters/second. A higher value is better. The slope of the change in PMCV is expressed as change in meters/second/52 weeks (one year).
Time frame: 96 weeks (expressed as a slope of change in meter/sec over 52 weeks)
Body Mass Index (BMI)
BMI change in kg/m2. BMI is a measure of weight relative to height. The slope of the change in BMI over the study was expressed as change in kg/m2/52 weeks.
Time frame: 96 weeks (slope of change in kg/m2/52 weeks)
Hemoglobin A1C
Slope of the Hemoglobin A1C change. A1C is measured in percent. It provides an estimate of how high blood sugar has been over the past three months. A higher value indicates poor diabetic control.
Time frame: The annual slope of the change in A1C over 96 weeks expressed in change in percent/52 weeks
Serum Triglycerides (TRG)
TRG change. TRG are a type of lipid or fat circulating in the blood. A higher value is associated with increased cardiovascular risk. The slope of the change in TRG was calculated as change in mg/dl over 52 weeks (one year).
Time frame: 96 weeks (slope of change mg/dl over 52 weeks)
LDL Cholesterol
LDL change. LDL is "bad" cholesterol, measured in mg/dL. A higher value is associated with elevated cardiovascular risk. A slope of change is calculated change in LDL in mg/dL/52 weeks (one year)
Time frame: 96 weeks (expressed as a slope of change in mg/dl/52 weeks)
HDL Cholesterol
HDL change. HDL is "good cholesterol", measured in mg/dL. A lower value is associated with higher cardiovascular risk. The slope of change is calculated as change in mg/dL/52 weeks (one year)
Time frame: 96 weeks (expressed as slope of change in mg/dL/52 weeks)
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