Intravenous Immunoglobulin Therapy for Small Fiber Neuropathy

• Status: Completed
• Trial end date: 2019-03-01
• Target enrollment: 0
• Participant gender: All

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.

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

Details

• Lead Sponsor: Academisch Ziekenhuis Maastricht
• Treatments: Antibodies; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Criteria

Patients can only participate when they are living in the Netherlands.

Inclusion Criteria:

• 18 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).

Exclusion Criteria:

• 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.