The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes
Diabetes Complications, Diabetes Mellitus, Diabetic Neuropathies
About this trial
This is an interventional treatment trial for Diabetes Complications focused on measuring Diabetes Complications, Diabetes Mellitus, Diabetic Neuropathies, IGIV-C, Immune Globulin Injection (Human), 10% Caprylate/Chromatography, Gamunex-C
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
Sites / Locations
- Beth Israel Deaconness Medical Center
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
0.9% Sodium Chloride
IGIV-C
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 5 days. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo).