A Randomized, Double-Blind Study of the Effects of
a Sustained Release Formulation of Sodium Nitrite
(SR-nitrite) on Patients with Diabetic Neuropathy
Authors: Soin Amol 
Published: October 2019

Background: Background: Sodium nitrite has been reported to be effective in reducing chronic
peripheral pain.
Objectives: To evaluate the safety and efficacy of 40 and 80 mg, BID, of an oral sustained release
formulation of sodium nitrite (SR-nitrite) in patients suffering from diabetic neuropathy, and to
determine whether SR-nitrite would reduce the frequency of headaches reported previously by
subjects receiving the same doses of an immediate release formulation.
Study Design: Phase II, single-center, randomized, double-blind, placebo controlled clinical trial.
Setting: The Ohio Pain Clinic and Kettering Medical Center.
Methods: Twenty-four patients were randomized to 40 mg or 80 mg SR-nitrite or placebo
twice daily for 12 weeks. The primary objective was to determine whether headaches would be
reduced using SR-nitrite. The primary efficacy endpoint was the mean difference in the change of
the Neuropathic Pain Symptom Inventory (NPSI) pain score from baseline to that reported after
12 weeks of treatment. Secondary endpoints included changes from baseline for the Brief Pain
Inventory (BPI) Scale, the RAND 36 questionnaire, Short Form McGill Questionnaire, daily patient
reported score for neuropathic pain, changes in HbA1c, PulseOx and quantitative sensory testing.
Results: The number of subjects reporting adverse events and the number of adverse events did not
change with dose. There were no reports of treatment-related headaches. Although no significant
differences were identified in patient responses to the questionnaires, a trend was observed. In
the NPSI assessment, patients in the 40 mg and 80 mg dose group reported a 12.7% and 22.0%
reduction in pain, respectively, compared to an 8.4% reduction by patients in the placebo group.
A trend was also observed with the BPI total severity score. However, the 40 mg dosing group
reported the greatest reduction in pain using the McGill Pain index and via patient logs of daily pain
scores, where the mean of pain scores reported by subjects in the 40 mg group dropped by day
41 and generally stayed lower than the mean of scores reported by subjects in either of the other
two groups. Patients in the 80 mg SR-nitrite group had an improvement in both Nerve Sensory
Conductance and Nerve Sensory Velocity. No changes were observed in HbA1c levels or PulseOx.
Limitations: Small sample size.
Conclusion: Sustained release sodium nitrite prevents the prevalent reports of headaches by
patients treated with an immediate release formulation of sodium nitrite. In a previous study of
patients with peripheral arterial disease (PAD), 40 mg BID treatment led to a statistically significant
reduction in reported pain, similar trends were observed at the end of the trial period for most of
the pain questionnaires used in the study. The 80 mg BID treatment had the more pronounced
affect on bioactivity (quantitative sensory testing), which was similar to the PAD study, where this
dose group had the greatest improvement in FMD {AU: spell out FMD}. The ability to alleviate pain
with BID treatment of SR-nitrite offers promise for a new non-addictive, non-sedating treatment of
chronic pain and warrants further study.
Key words: diabetes, diabetic neuropathy, neuropathic pain, peripheral neuropathy, sodium nitrite