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

NCT02915263 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 2016P000166
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies

Keywords

Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; IGIV-C; Immune Globulin Injection (Human), 10% Caprylate/Chromatography; Gamunex-C

Outcome Measures

Primary Outcomes (2)

• Change in Sensory Neuropathy as Measured by the Utah Early Neuropathy Score (UENS).

  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. The UENS scale ranges from 0 (no neuropathy) to 42 (severe small fiber neuropathy). The outcome measure is the UENS score from 7 weeks (final evaluation) minus the UENS score from the baseline visit. A positive value indicates that neuropathy worsened over the course of the trial (a worse outcome), a negative score indicates that neuropathy improved over the course of the trial (a better outcome).

  7 weeks after first infusion.

• Change in Neuropathic Pain Severity as Measured by the Pain Visual Analogue Scores (VAS).

  The visual analog scale (VAS) of pain allows for quantification of neuropathic pain. The VAS pain scale is a line with markings that range from 0 (no pain) to 10 (worse pain), with whole digit intervals (thus an 11 point scale). This outcome measure is the VAS pain score at the final visit (7 weeks after first infusion) minus the VAS pain score at the baseline visit. A positive result indicates that pain increased over the course of the study (a worse outcome), a negative result indicates that pain improved over the course of the trial (a better outcome).

  7 weeks after first infusion

Secondary Outcomes (2)

• Change in Neuropathy Severity as Measured by Skin Biopsies.

  7 weeks after first infusion

• Change in Autonomic Neuropathy as Measured by Standardized Autonomic Nervous System Testing.

  7 weeks after first infusion

Study Arms (2)

0.9% Sodium Chloride

PLACEBO COMPARATOR

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

IGIV-C

EXPERIMENTAL

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

Interventions

IGIV-C DRUG

Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.

Also known as: Gamunex-C Liquid, Immune globulin injection (human), 10% caprylate/chromatography purified

IGIV-C

0.9% Sodium Chloride DRUG

Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.

Also known as: Saline, 0.9%NaCl

0.9% Sodium Chloride

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Female subjects of childbearing potential with a positive urine pregnancy test.
• BMI \>30.
• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Grifols Biologicals, LLC: collaborator

Study Sites (1)

Beth Israel Deaconness Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (22)

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MeSH Terms

Conditions

Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies

Interventions

Immunoglobulins; Caprylates; Sodium Chloride

Condition Hierarchy (Ancestors)

Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Christopher Gibbons MD
• Organization: Beth Israel Deaconess Medical Center

cgibbons@bidmc.harvard.edu

617-632-8454

Study Officials

• Christopher Gibbons, MD

  Beth Israel Deaconess Medical Cednter

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: September 27, 2016
• Study Start: September 11, 2017
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: May 7, 2024
• Results First Posted: September 13, 2023

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)