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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01480297
Recruitment Status : Completed
First Posted : November 28, 2011
Results First Posted : April 24, 2015
Last Update Posted : April 24, 2015
Information provided by (Responsible Party):
Rodica Pop-Busui, University of Michigan

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.

Condition or disease Intervention/treatment Phase
Peripheral Neuropathy Type 1 Diabetes Drug: Salsalate Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2011
Actual Primary Completion Date : April 2012
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Salsalate
All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner).
Drug: Salsalate
Salsalate 3 grams daily (1 gram TID with meals)
Other Name: Salsalate (Amneal Pharmaceuticals)

Primary Outcome Measures :
  1. Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm [ Time Frame: Baseline and 12 weeks ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01480297

United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Principal Investigator: Rodica Pop-Busui, MD, PhD University of Michigan, Department of Internal Medicine

Responsible Party: Rodica Pop-Busui, Associate Professor of Internal Medicine, University of Michigan Identifier: NCT01480297     History of Changes
Other Study ID Numbers: SALP
First Posted: November 28, 2011    Key Record Dates
Results First Posted: April 24, 2015
Last Update Posted: April 24, 2015
Last Verified: April 2015

Keywords provided by Rodica Pop-Busui, University of Michigan:
Diabetes type 1

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Peripheral Nervous System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Neuromuscular Diseases
Nervous System Diseases
Salicylsalicylic acid
Sodium Salicylate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action