Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy
Condition: Peripheral Neuropathy; Type 1 Diabetes
MeSH terms: Peripheral Nervous System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Salsalate
Intervention type(s): Drug
Intervention description(s): Salsalate 3 grams daily (1 gram TID with meals)
Other intervention name(s): Salsalate (Amneal Pharmaceuticals)
Intervention MeSH terms: Salicylsalicylic acid; Sodium Salicylate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pain; Neuropathy; Diabetes type 1