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

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ClinicalTrials.gov Identifier: NCT02915263
Recruitment Status : Recruiting
First Posted : September 27, 2016
Last Update Posted : December 7, 2018
Sponsor:
Collaborator:
Grifols Biologicals, LLC
Information provided by (Responsible Party):
Christopher Gibbons, MD, Beth Israel Deaconess Medical Center

Brief 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.


Condition or disease Intervention/treatment Phase
Diabetes Complications Diabetes Mellitus Diabetic Neuropathies Drug: IGIV-C Drug: 0.9% Sodium Chloride Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled Trial To Evaluate The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes
Actual Study Start Date : September 11, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: 0.9% Sodium Chloride
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.
Drug: 0.9% Sodium Chloride
Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
Other Names:
  • Saline
  • 0.9%NaCl

Experimental: IGIV-C
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).
Drug: IGIV-C
Gamunex-C [immune globulin injection (human) 10% caprylate/chromatography purified] is a sterile solution of human immune globulin protein.
Other Names:
  • Gamunex-C Liquid
  • Immune globulin injection (human), 10% caprylate/chromatography purified




Primary Outcome Measures :
  1. Change in sensory neuropathy as measured by the Utah Early Neuropathy Score (UENS). [ Time Frame: 7 weeks after first infusion ]
    The Utah Early Neuropathy Scale (UENS) was developed specifically to detect and quantify early small-fiber sensory neuropathy and to recognize modest changes in sensory severity and distribution.

  2. Change in neuropathic pain severity as measured by the pain visual analogue scores (VAS). [ Time Frame: 7 weeks after first infusion ]
    The visual analog scale (VAS) of pain allows for quantification of neuropathic pain (line from 0: no pain to 10:worst pain)


Secondary Outcome Measures :
  1. Change in neuropathy severity as measured by skin biopsies. [ Time Frame: 7 weeks after first infusion ]
    Skin biopsies will be evaluated by measuring the Intra-epidermal nerve fiber density

  2. Change in Autonomic Neuropathy as measured by standardized autonomic nervous system testing. [ Time Frame: 7 weeks after first infusion ]
    The standardized autonomic nervous system testing evaluates the heart rate variability to paced breathing, the heart rate and blood pressure response to the Valsalva maneuver, the blood pressure response to tilt table testing, and sudomotor function testing.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02915263


Contacts
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Contact: Sharika Rajan, MD 6176328964 srajan@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconness Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Christopher Gibbons, MD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Grifols Biologicals, LLC
Investigators
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Principal Investigator: Christopher Gibbons, MD Beth Israel Deaconess Medical Cednter

Publications:

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Responsible Party: Christopher Gibbons, MD, Associate Professor of Neurology, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02915263     History of Changes
Other Study ID Numbers: 2016P000166
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Christopher Gibbons, MD, Beth Israel Deaconess Medical Center:
Diabetes Complications
Diabetes Mellitus
Diabetic Neuropathies
IGIV-C
Immune Globulin Injection (Human), 10% Caprylate/Chromatography
Gamunex-C
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Diabetic Neuropathies
Diabetes Mellitus
Diabetes Complications
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Neuromuscular Diseases
Nervous System Diseases
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs