Phase IIa: Safety, PK, & Tolerability of Sodium Nitrite in Patients With Peripheral Arterial Disease-SONIC
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Intervention: sodium nitrite
Intervention description: 0, 40 or 80 mg twice each day for 10 weeks followed by a 1 week escalation of 2 times the dose.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 55.0
Sex: All
Minimum age: 35 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      Sodium nitrite has been demonstrated to promote new blood vessel growth, speed up wound
      healing and prevent tissue necrosis in animals. Since patients with PAD experience many of
      these problems, this study will seek to determine whether this drug, when given orally, could
      provide the same benefits to patients with PAD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject is between and including 35 and 85 years of age.

          -  Subjects must be either male or females post-menopausal, sterilized or using suitable
             birth control. Suitable birth control must be total abstinence, male partner
             sterilization or double barrier method paired with using oral contraception,
             injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring,
             percutaneous contraceptive patches, or intrauterine device (IUD).

          -  History of Peripheral Arterial Disease (PAD) confirmed by medical chart or an ankle
             brachial pressure index at rest ≤0.90.

          -  If receiving medical standard treatment for cardiac risk factors, subject must have
             been on a stable treatment for at least 1 month prior to Screening. Treatments must
             have not changed significantly in the last month and are not expected to change over
             the duration of the study.

          -  If subjects experience claudication symptoms, subjects must have stable lower
             extremity symptoms for at least 1 month prior to Screening.

          -  Ability to provide written informed consent and willingness as documented by a signed
             informed consent form.

        Exclusion Criteria:

          -  Non-atherosclerotic PAD.

          -  Lower extremity surgical or percutaneous revascularization, evidence of graft failure
             or other peripheral vascular surgical procedure within last 6 months prior to
             Screening.

          -  Anticipated lower extremity revascularization within the treatment period.

          -  Myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic
             attack within 3 months prior to Screening.

          -  Poorly controlled diabetes (HgA1c > 10.0).

          -  Poorly controlled hypertension (systolic blood pressure (SBP) ≥ 160 mmHg or diastolic
             blood pressure (DBP) ≥ 100 mmHg) despite therapy.

          -  Systolic blood pressure ≤100 mmHg on current medical regimen.

          -  Hypersensitivity to sodium nitrite or related compounds.

          -  Renal insufficiency documented as eGFR < 30 mL/minute/1.73 m2.

          -  Pregnant or nursing women.

          -  Life expectancy < 6 months.

          -  A chronic illness that may increase the risks associated with this study in the
             opinion of the investigator.

          -  Active malignancy requiring active anti-neoplastic therapy that will, in the opinion
             of the investigator, interfere with study treatment or participation.

          -  Active infection.

          -  NYHA CHF Class III or IV.

          -  Recent hospitalization (< 30 days) for acute coronary syndrome, myocardial infarction,
             congestive heart failure or stroke.

          -  Recent (< 30 days) coronary revascularization.

          -  Previously treated with angiogenic factors or stem cell therapy within 1 year prior to
             Screening.

          -  Involvement in another PAD clinical trial within past 1 month prior to Screening.

          -  Exposed tendon, muscle or bone or a diagnosis of critical leg ischemia.

          -  Previous amputation within 3 months prior to Screening or planned amputation that
             would limit walking (e.g. small toe is allowed).

          -  The subject's ability to perform the 6 minute walk test is limited by symptoms other
             than claudication.

          -  Current diagnosis of alcohol or other substance abuse.

          -  History of methemoglobinemia, [met-Hb > 15%].

          -  Inability to speak English (due to need to administer standardized English-language
             questionnaire).

          -  Evidence of anemia.

          -  History of chronic hemolytic condition, including sickle cell disease.

          -  Chronic use of anti-migraine medication such as Imitrex or sumatriptan.

          -  Have a positive screen for glucose-6-phosphate dehydrogenase deficiency at screening.

          -  Subjects who regularly take the following medications: Allopurinol, PDE-5 inhibitors,
             sedative tricyclic antidepressants, antihistamines, meperidine and related central
             nervous system depressants, and nitrates.