Topiramate for Cryptogenic Sensory Peripheral Neuropathy (TopCSPN)

The TopCSPN trial is a double blinded randomized placebo controlled study of oral topiramate
as a potential disease altering 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.

Eligibility Criteria

Inclusion Criteria

1. Age 18-75

2. Neuropathy (pain, tingling, pins or needles, burning, etc.) in your extremities (arms, legs, hands, feet) 

3. No current or prior history of therapy with topiramate (Topamax).

4. 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.

5. 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. Any identified 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 immunofixation.

2. Diagnosis of diabetes by history, or screening laboratory results including: HgA1c ≥
6.5%, fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L), or 2-hour oral glucose
tolerance ≥ 200 mg/dL (11.1 mmol/L). Borderline screening labs can be repeated within
two weeks with PPI approval.

3. History of nephrolithiasis or use of ongoing preventative treatment.

4. Family history of a non-diabetic neuropathy in a first-degree relative.

5. Severe neuropathy: Utah Early Neuropathy Score > 24 at screening

6. Active foot ulceration or a history of a nontraumatic foot amputation.

7. ECG with QTc more than 450 ms in men, or 470 ms in women.

8. Current or planned therapeutic anticoagulation including coumadin or oral factor X or
thrombin inhibitor therapy (anti-platelet agents are permissible).

9. Chronic corticosteroid use excluding topical treatment.

10. Use of a carbonic anhydrase inhibitor (such as acetazolamide) due to risk of
nephrolithiasis.

11. Planned bariatric surgery

12. Use of other weight loss medications.

13. Use of neuropathic pain agents beyond first line agents (permissible first line agents
include gabapentin, pregabalin, tricyclic antidepressants, duloxetine, venlafaxine,
tramadol less than 200 mg daily, or topical lidocaine).

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 values above normal limits as follows: AST/ALT ≥1.5 times upper
limit normal, 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
investigator, 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.

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.

Principal Investigator

Mamatha Pasnoor, MD

Study Contact

Alyssa Lackey, 913-945-9942, alackey@kumc.edu

Estimated Completion Date

Friday, March 1, 2019

ClinicalTrials.gov #

NCT02878798
03/26/2018