Intravenous Immunoglobulin Therapy for Small Fiber Neuropathy

NCT02637700 | Completed Phase 2 DMC

• 2 other identifiers: IVIg-SFN2015-002624-31
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Small fiber neuropathy (SFN) is the most common cause of neuropathic pain in peripheral neuropathies, with a prevalence of at least 53/100.000. Patients with SFN may have excruciating pain and current anti-neuropathic and other pain drugs do not relief pain substantially. Several studies suggested an immunological basis in SFN and case studies have reported efficacy of treatment with intravenous immunoglobulin (IVIg) in patients with SFN. It is therefore conceivable that immunological mechanisms play a role in idiopathic SFN (I-SFN). However, to date no randomized controlled study with IVIg in patients with SFN has been performed. The aim of the current study is to investigate the efficacy and safety of IVIg in patients with I-SFN in a randomized, double-blind, placebo-controlled study. The objective of the study is to evaluate the efficacy of IVIg treatment (4 courses of treatment, 3 weeks apart) compared to placebo on pain alleviation.

Conditions

Small Fiber Neuropathy

Keywords

Small Fiber Neuropathy; Painful Neuropathy; Intravenous Immunoglobulin Therapy

Outcome Measures

Primary Outcomes (1)

• Change in Pain Intensity Numerical Rating Scale (PI-NRS)

  Mean weekly pain intensity is assessed twice a week for a period of three months

Secondary Outcomes (9)

• Change in Pain Intensity Numerical Ratings Scale (PI-NRS)

  The nocturnal pain intensity will be assessed twice a week for a period of three months

• Patient Global Impression of Change (PGIC)

  The global impression of change will be measured 5 times in three months

• Change in Small Fiber Neuropathy Symptoms Inventory Questionnaire (SFN-SIQ)

  This will be measured 5 times in three months

• Change in Neuropathic Pain Scale (NPS)

  This will be measured 5 times in three months

• Change in Small Fiber Neuropathy Rasch-Built Overall Disability Scale (SFN-RODS)

  This will be measured 5 times in three months

Study Arms (2)

Intravenous Immunoglobulin

EXPERIMENTAL

Patients with skin biopsy proven idiopathic Small Fiber Neuropathy in this arm will receive intravenous immunoglobulin.

Drug: Intravenous Immunoglobulin

Placebo (Saline 0.9%)

PLACEBO COMPARATOR

Patients with skin biopsy proven idiopathic Small Fiber Neuropathy in this arm will receive placebo (saline 0.9%).

Drug: Placebo

Interventions

Intravenous Immunoglobulin DRUG

Comparison between intravenous immunoglobulin and placebo (saline 0.9%).

Also known as: Gamunex

Intravenous Immunoglobulin

Placebo DRUG

Comparison between placebo (saline 0.9%) and intravenous immunoglobulin.

Also known as: Saline (0.9%)

Placebo (Saline 0.9%)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older.
• Skin-biopsy proven idiopathic SFN or idiopathic painful neuropathy with predominantly SFN pattern
• Pain intensity rated ≥ 5 on the PI-NRS (maximum pain) or on the neuropathic pain scale,36,37 question number 1 for at least 12 weeks before the study as declared by each patient to the best of their knowledge; if available, medical records of each patient will be consulted on the reported pain intensity.
• Each subject will receive an information leaflet and an informed consent form. Subjects must give informed consent by signing and dating prior to study entry.
• Eligible patients must be willing to complete all study-related activities and examination required by the protocol (see Tables 1-4).

You may not qualify if:

• Are unable or unwilling to provide written informed consent.
• Have predominant clinical picture of large nerve fiber involvement (i.e., weakness, loss of vibration sense, hypo-/areflexia).
• Had treatment with IVIg or any other immunomodulatory/immunosuppressive agents (e.g., steroids) within the last 12 weeks prior to the date of informed consent.
• Have an underlying cause of SFN (diabetes, SCN9A/10A/11A mutations, hypothyroidism, renal failure, vitamin B12 deficiency, monoclonal gammopathy, alcohol abuse (more than 5 IU/day), malignancies, drugs that cause neuropathy (e.g. chemotherapy, amiodarone, propafenone)).
• Have a history of anaphylaxis or severe systemic response to immunoglobulin or with a blood product.
• Have cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, or history of congestive heart failure, severe hypertension (diastolic blood pressure \>120 mmHg or systolic \>170 mmHg).
• Are females who are pregnant, breast-feeding, or if of childbearing potential, or unwilling to practice adequate contraception throughout the study.
• Have known hyperviscosity.
• Have a history of renal insufficiency or high serum creatinine levels (MDRD \<30).
• Have known selective immunoglobulin A (IgA) deficiency.
• Have conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
• Have a known hypercoagulable state.
• Are mentally challenged adult subjects unable to give independent informed consent.
• The use of pain (analgesic/anti-neuropathic) medication is allowed, but only if dosages are remained unchanged for at least 30 days prior to randomization. A change in dosage of these drugs will not be allowed throughout the study.

Sponsors & Collaborators

• Academisch Ziekenhuis Maastricht: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Netherlands

Location

Related Publications (2)

• Geerts M, de Greef BTA, Sopacua M, van Kuijk SMJ, Hoeijmakers JGJ, Faber CG, Merkies ISJ. Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy. Neurology. 2021 May 18;96(20):e2534-e2545. doi: 10.1212/WNL.0000000000011919. Epub 2021 Mar 25.

  PMID: 33766992 DERIVED

• de Greef BT, Geerts M, Hoeijmakers JG, Faber CG, Merkies IS. Intravenous immunoglobulin therapy for small fiber neuropathy: study protocol for a randomized controlled trial. Trials. 2016 Jul 20;17(1):330. doi: 10.1186/s13063-016-1450-x.

  PMID: 27439408 DERIVED

MeSH Terms

Conditions

Small Fiber Neuropathy; Neuropathy, Painful

Interventions

Immunoglobulins, Intravenous; Sodium Chloride

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Catharina G Faber, MD, PhD

  Academisch Ziekenhuis Maastricht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 22, 2015
• Study Start: July 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: July 5, 2019

Record last verified: 2019-07

Locations

NL (1)