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Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy (SALP)

Primary Purpose

Peripheral Neuropathy, Type 1 Diabetes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Salsalate
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Neuropathy focused on measuring Pain, Neuropathy, Diabetes type 1

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Type 1 diabetes (T1D)
  • Peripheral neuropathy with symptoms of pain, or with other uncomfortable symptoms (e.g., burning, prickling).
  • 18 to 70 years old
  • Stable insulin treatment program for at least the past 3 months.
  • Abnormal nerve conduction studies (based on study screening examination)
  • Willing and able to take an oral (by mouth) medication 3 times per day for 3 months.
  • WOMEN using an appropriate method of contraception during the course of the study (hormonal, IUD, or diaphragm.
  • Willing and able to provide written informed consent for study participation.

Exclusion Criteria:

  • Neuropathy from a cause other than diabetes.
  • Allergy to salsalate or similar medications (aspirin, non-steroidal anti-inflammatory medicines like ibuprofen and naproxen).
  • Currently on blood thinning agents such as Coumadin, Heparin, Plavix, Pradaxa, high-dose aspirin (more than 325 mg daily).
  • Any severe low blood sugar episodes in the past 6 months (needed assistance to treat).
  • Diabetic ketoacidosis in the past 6 months.
  • Severe neuropathy, or have had an ulcer or amputation on either foot or either leg.
  • Creatinine level (a measure of kidney function is greater than 1.4 mg/dl (for women) or greater than 1.5 mg/dl (for men) or your estimated GFR is under 60.
  • Albumin in your urine or other signs of reduced kidney function.
  • Liver enzymes (including ALT, AST and Bilirubin) levels are more than 2 and ½ times the upper limit of normal.
  • Blood platelets are less than 100,000 at the time of screening.
  • Organ transplant (lung, kidney, heart, pancreas, liver).
  • Chronic immunosuppressive therapy, for example, daily prednisone or other steroids, methotrexate, Imuran, CellCept. This includes daily, or recurrent use of oral steroids used to treat asthma.
  • Regular NSAID medications (e.g., Naproxen, Ibuprofen) use. If used occasionally, you will be asked to not use them during the study.
  • History of drug or alcohol abuse, or if you take more than 10 alcoholic drinks per week.
  • History of stomach ulcers or bleeding from your bowel.
  • Heart attack, heart bypass surgery, heart failure or a stroke EVER.
  • Current treatment for any cancer (other than basal cell or squamous cell skin cancer).
  • Treatment with lithium.
  • Ever had Reyes' syndrome.
  • Pregnant, nursing, or planning to become pregnant during the time of the study.
  • Allergic to lidocaine or epinephrine (used for numbing skin prior to biopsies).
  • Keloid scarring in the past.
  • Receiving other experimental treatments.

Sites / Locations

  • University of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Salsalate

Arm Description

All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner).

Outcomes

Primary Outcome Measures

Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm
Intra-epidermal Nerve Fiber Density (IENFD) was measured at two anatomic locations (thigh and ankle) at baseline and after 12 weeks of treatment with Salsalate. IENFD is expressed as fibers per mm. Means and standard deviations are shown.

Secondary Outcome Measures

Full Information

First Posted
November 23, 2011
Last Updated
April 23, 2015
Sponsor
University of Michigan
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1. Study Identification

Unique Protocol Identification Number
NCT01480297
Brief Title
Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy
Acronym
SALP
Official Title
A Pilot Study to Determine the Effects of 12 Weeks of Treatment With Salsalate on Measures of Peripheral Neuropathy in Type 1 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This 12 week study will examine the effects of daily Salsalate treatment on markers of neuropathic pain and intra-epidermal nerve fiber density. the study is being done in people with type 1 diabetes with signs and symptoms of peripheral neuropathy.
Detailed Description
This project will be used to establish preliminary data for a planned NIH-sponsored multicenter study of the effects of salsalate on diabetic neuropathy (DN) in people with type 1 diabetes. Diabetic peripheral neuropathy (DN) ultimately affects one-half of the patients with type 1 diabetes (T1DM) and is a major cause of disability, high mortality, and poor quality of life. Although intensive glucose control has proven efficacy in delaying or preventing DN in T1DM and type 2 diabetes (T2DM), most people with diabetes do not reach and maintain glycemic levels needed to achieve these benefits. In addition, many patients with diabetes still develop diabetic complications, including DN, despite good glucose control. For DN, no disease modifying treatment other than glycemic control is available. Therefore, it is essential to identify new drug targets and to treat DN as early as possible in its course. The investigators planned, multi-center study will be the first to determine the effect of an anti-inflammatory agent, salsalate, on DN development and progression, and on DN pain in type 1 diabetes. This proof-of-concept pilot study will measure the effects of short term (12 week) treatment with Salsalate on novel and on established measures of peripheral neuropathy. Ultimately, this may permit measurement of treatment effects over a shorter period of time than by using established measures such as nerve conduction studies. Salsalate, a prodrug form of salicylate, is used to treat osteoarthritis and other rheumatologic conditions. It is highly effective in modulating the IKKβ/NF-κB pathway, with a large margin of safety, and has a glucose lowering effect in patients with type 2 diabetes. The IKKβ/NF-κB pathway is unique in that it is implicated in both the pathogenesis of nerve fiber loss as well as pain in DN. The proposed study design employs a quantifiable early measure of DN, IENFD of the thigh, allowing for accurate assessment of actual nerve fiber density over time. In the pilot study, biomarkers of pain found in IENF's as well as IENFD will be measured pre and post 3 months of treatment with Salsalate, 3 grams daily.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Neuropathy, Type 1 Diabetes
Keywords
Pain, Neuropathy, Diabetes type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Salsalate
Arm Type
Experimental
Arm Description
All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner).
Intervention Type
Drug
Intervention Name(s)
Salsalate
Other Intervention Name(s)
Salsalate (Amneal Pharmaceuticals)
Intervention Description
Salsalate 3 grams daily (1 gram TID with meals)
Primary Outcome Measure Information:
Title
Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm
Description
Intra-epidermal Nerve Fiber Density (IENFD) was measured at two anatomic locations (thigh and ankle) at baseline and after 12 weeks of treatment with Salsalate. IENFD is expressed as fibers per mm. Means and standard deviations are shown.
Time Frame
Baseline and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Type 1 diabetes (T1D) Peripheral neuropathy with symptoms of pain, or with other uncomfortable symptoms (e.g., burning, prickling). 18 to 70 years old Stable insulin treatment program for at least the past 3 months. Abnormal nerve conduction studies (based on study screening examination) Willing and able to take an oral (by mouth) medication 3 times per day for 3 months. WOMEN using an appropriate method of contraception during the course of the study (hormonal, IUD, or diaphragm. Willing and able to provide written informed consent for study participation. Exclusion Criteria: Neuropathy from a cause other than diabetes. Allergy to salsalate or similar medications (aspirin, non-steroidal anti-inflammatory medicines like ibuprofen and naproxen). Currently on blood thinning agents such as Coumadin, Heparin, Plavix, Pradaxa, high-dose aspirin (more than 325 mg daily). Any severe low blood sugar episodes in the past 6 months (needed assistance to treat). Diabetic ketoacidosis in the past 6 months. Severe neuropathy, or have had an ulcer or amputation on either foot or either leg. Creatinine level (a measure of kidney function is greater than 1.4 mg/dl (for women) or greater than 1.5 mg/dl (for men) or your estimated GFR is under 60. Albumin in your urine or other signs of reduced kidney function. Liver enzymes (including ALT, AST and Bilirubin) levels are more than 2 and ½ times the upper limit of normal. Blood platelets are less than 100,000 at the time of screening. Organ transplant (lung, kidney, heart, pancreas, liver). Chronic immunosuppressive therapy, for example, daily prednisone or other steroids, methotrexate, Imuran, CellCept. This includes daily, or recurrent use of oral steroids used to treat asthma. Regular NSAID medications (e.g., Naproxen, Ibuprofen) use. If used occasionally, you will be asked to not use them during the study. History of drug or alcohol abuse, or if you take more than 10 alcoholic drinks per week. History of stomach ulcers or bleeding from your bowel. Heart attack, heart bypass surgery, heart failure or a stroke EVER. Current treatment for any cancer (other than basal cell or squamous cell skin cancer). Treatment with lithium. Ever had Reyes' syndrome. Pregnant, nursing, or planning to become pregnant during the time of the study. Allergic to lidocaine or epinephrine (used for numbing skin prior to biopsies). Keloid scarring in the past. Receiving other experimental treatments.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rodica Pop-Busui, MD, PhD
Organizational Affiliation
University of Michigan, Department of Internal Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

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Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy

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