| Eligibility |
Inclusion Criteria
1. T1DM;
2. age 18-70;
3. mild DN as defined by symptoms and/or signs, confirmed by at least one abnormality in
electrophysiology studies (abnormality of at least one attribute among conduction
velocity, latency, amplitude or F-Wave in at least one nerve among sural sensory,
ulnar sensory, or peroneal motor);
4. sural nerve amplitude > 0 µV. If sural nerve amplitude is 0 µV (unrecordable) peroneal
motor nerve conduction velocity must be = 35 m/second*;
5. on a stable insulin regimen for the 3 months prior to enrollment;
6. be willing and capable of signing the IRB approved consent form and willing and able
to cooperate with the medical procedures for the study duration;
7. be willing to accept random treatment assignment to salsalate or placebo; and
8. women of childbearing age agree to use an appropriate contraceptive method (hormonal,
IUD, or diaphragm) for the duration of the study and must have a negative urine
pregnancy test at screening.
Exclusion Criteria
1. history of severe DN, active lower limb ulceration or lower limb amputation directly
caused by diabetic neuropathy, or risk factors for any other causes of neuropathy
(e.g. active hepatitis C, end stage renal disease, systemic lupus erythematosus or a
known hereditary neuropathy) as determined through medical history, family history,
history of medications, occupational history, history of exposure to toxins, physical
and neurological examinations);
2. history of recent severe hypoglycemia (within prior 6 months) as defined by
hypoglycemia resulting in coma or seizure or a history of recurrent diabetic
ketoacidosis (DKA) or any diabetic ketoacidosis within the last three months.
3. history of persistent macroalbuminuria [random urine microalbumin creatinine ratio
(ACR) >300 mg/gm]. ACR up to 300 mg/gm is acceptable if serum creatinine is <1.4 for
women, <1.5 for men AND estimated GFR (eGFR) is > 60;
4. serum creatinine >1.4 for women and >1.5 for men or eGFR <60 [possible chronic kidney
disease stage 3 or greater calculated using the Modification of Diet in Renal Disease
(MDRD) equation];
5. pregnancy or lactation, or intention to become pregnant in next 12 months;
6. history of previous lung, kidney, pancreas, liver, cardiac or bone marrow transplant;
7. history of drug or alcohol abuse within the previous 5 years, or current weekly
alcohol consumption >10 units/week;
8. use of warfarin (Coumadin), clopidogrel (Plavix), dipyridamole (Persantine), heparin
or other anticoagulants, probenecid (Benemid, Probalan), sulfinpyrazone (Anturane) or
other uricosuric agents; Subjects must agree to not use high-dose aspirin during the
course of the study. Daily low-dose aspirin treatment (not more than 81 mg per day)
may be continued if currently prescribed.
9. requiring long-term glucocorticoid therapy or chronic immunosuppressive therapy;
Inhaled steroid use for management of asthma is not an absolute exclusion.
10. use of lithium
11. participation in an experimental medication trial within 3 months of starting the
study;
12. current therapy for malignant disease other than basal- cell or squamous-cell skin
cancer;
13. history of gastrointestinal bleeding or active gastric ulcer; screening laboratory
abnormalities including AST (SGOT) and or ALT (SGPT) > 2.5 x the upper limit of normal
(ULN), total bilirubin > 1.5 x ULN, platelets < 100,000;
14. You have developed keloid scarring in the past. Keloids are large, thick masses of
scar tissue. These are more common among dark-skinned people.
15. presence of any condition that, in the opinion of the investigator would make it
unlikely for the subject to complete 12 months of study participation, e.g., history
of non- adherence to therapeutic regimens, presence of conditions likely to limit life
expectancy, living situation that would interfere with study visit schedules such as a
job requiring frequent or extended travel
16. known hypersensitivity to salsalate. Patients who have experienced asthma, hives, or
other allergic-type reactions to aspirin or other NSAIDs are excluded from
participation. Patients with known or suspected aspirin or NSAID-sensitive asthma are
excluded.
In addition, subjects with concurrent chicken pox, influenza, flu-like symptoms or other
symptomatic viral illnesses should not be enrolled in the study until the illness or
condition has resolved.
Subjects with known or suspected hypersensitivity to lidocaine or epinephrine may not be
able to participate as these agents are used for local anesthesia during skin biopsies. The
study investigators should consider the nature and severity of past reported reactions to
these agents, and may consider alternative anesthesia options for local anesthesia on a
case by case basis.
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