The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes
Condition: Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies
MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies; Diabetes Mellitus; Diabetes Complications
Intervention: IGIV-C; 0.9% Sodium Chloride
Intervention description: Gamunex-C [immune globulin injection (human) 10% caprylate/chromatography purified] is a sterile solution of human immune globulin protein.; Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
Intervention MeSH terms: Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; IGIV-C; Immune Globulin Injection (Human), 10% Caprylate/Chromatography; Gamunex-C

Summary:

      The goal of this pilot study is to obtain preliminary data on the magnitude of the treatment
      effect of IVIG on the neuropathic pain and neuropathy severity associated with treatment
      induced neuropathy (TIND).

      The investigators hypothesize that immune globulin, administered intravenously (IVIG), will
      reduce the pain associated with treatment induced neuropathy and reduce the neuropathy
      severity.

      Treatment induced neuropathy in diabetes, is an iatrogenic complications of diabetes. The
      preliminary data will be used to power a larger treatment trial, and to aid the understanding
      of the mitigating factors in the treatment response.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Individuals with a diagnosis of diabetes and treatment induced neuropathy (defined by
             the onset of neuropathic pain and signs of small fiber or autonomic neuropathy within
             8 weeks of a change in HbA1C exceeding 3 points over 3 months).

          -  Ages 18-60.

          -  BMI ≤ 30.

          -  Nonsmoker.

          -  Consumption of up to 4 alcoholic beverages per week.

          -  No history of substance abuse or dependence with 1 year prior to screening.

          -  Normal ECG.

          -  Vital Signs within normal range (with the exception of a resting tachycardia which is
             expected in all subjects due to neuropathic pain; research subjects with a heart rate
             greater than 110 bpm, however, will be excluded).

          -  CBC, standard chemistry panel within normal limits.

          -  Standard coagulation studies (within BIDMC laboratory normal limits) including PT,
             PTT, platelets.

          -  D-dimer <0.05 FEU.

        Exclusion Criteria:

          -  Female subjects of childbearing potential with a positive urine pregnancy test.

          -  BMI >30.

          -  No other known cause of neuropathy (chemotherapy, toxins, other medical disorder - all
             subjects have diabetes so this would not be an exclusionary factor).

          -  Anticoagulation with warfarin, aspirin & Plavix together or other anticoagulant that
             would place subjects at undue risk of bleeding from a skin biopsy. Aspirin or Plavix
             alone are not an exclusion criterion.

          -  Clinically active coronary artery or cerebrovascular disease.

          -  Cardiac insufficiency (NYHA Grade III-IV), cardiomyopathy, significant cardiac
             dysrhythmia requiring treatment, unstable advanced ischemic heart disease.

          -  History of congenital or acquired coagulopathy or thromboembolic disease before the
             age of 55 or arterial thromboembolic disease before the age of 45.

          -  History of Deep Venous Thrombosis (DVT) and/or Pulmonary Embolism (PE).

          -  Evidence of lower extremity deep vein thrombosis at screening including limb swelling,
             pain or discoloration and or risk of thrombotic event as assessed by Wells criteria.

          -  Known history of blood hyperviscosity.

          -  Evidence of severe vascular disease (history of ulceration, poor wound healing,
             vascular claudication).

          -  History of allergic reaction to local anesthesia for skin biopsies or history of
             scarring or keloid formation.

          -  History of renal dysfunction that includes glomerular filtration rate <60 mL/min, or
             creatinine of >2.0 mg/dL.

          -  Known IGA deficiency with antibodies to IgA.

          -  History of hypersensitivity, anaphylaxis or severe systemic response to
             immunoglobulin, blood or plasma derived products.

          -  Positive Direct Antiglobulin Test (DAT) prior to administration or history of
             hemolytic anemia.

          -  Subject who is unlikely to comply with the study protocol, or in the opinion of the
             investigator, would not be a suitable candidate for participation in the study.

        Criteria for discontinuation:

          -  Pregnancy: women of childbearing potential will have a urine pregnancy test at every
             visit. Subjects who become pregnant will be discontinued from the study.

          -  A Grade 3 or higher allergic reaction within 24 hours of IVIG/Placebo infusion.

          -  Any thromboembolic events (e.g. myocardial infarction, stroke, venous thromboembolism)

          -  Clinically significant hematologic complications (e.g. hemolysis and/or neutropenia).

          -  Withdrawal by subject