The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes

• Status: Recruiting
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beth Israel Deaconess Medical Center
• Collaborator: Grifols Biologicals, LLC
• Treatments: Antibodies; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

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