IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3
Condition: Small Fiber Neuropathy; Idiopathic Peripheral Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Small Fiber Neuropathy
Intervention: Intravenous immunoglobulin; 0.9% Sodium Chloride
Intervention description: Gamunex-C [immune globulin injection (human) 10% caprylate/chromatography purified] is a sterile solution of human immune globulin protein.; Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Healthy volunteers: No
Keywords: small Fiber Neuropathy; Idiopathic Peripheral Neuropathy; IVIg; Gamunex-C

Summary:

      The objective of this study is to develop a rationale for the selective treatment of small
      fiber neuropathy with immune globulin (IVIG) in the appropriate patients.

      The investigators hypothesize that individuals with auto-antibodies targeting neuronal
      antigens (TS-HDS and FGFR3) and confirmed evidence of small fiber neuropathy (by skin biopsy
      analysis of intra-epidermal nerve fiber density) will have an improvement in both nerve fiber
      density and pain after treatment with immune globulin.

      The co-primary endpoints will be a change in neuropathic pain (by VAS pain score) and a
      change in intra-epidermal nerve fiber density (by punch skin biopsy).

      The data gained from this pilot study will establish a rationale, with an appropriate
      screening test, for the use of immune globulin for the treatment of small fiber neuropathy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient with clinically evident and biopsy proven pure small fiber neuropathy as
             evidenced by reduced intra-epidermal nerve fiber density seen on skin biopsy using PGP
             9.5 as the immunostain.

          2. Patients must have a baseline pain score on a VAS scale of Greater or equal to 4/10

          3. Patients must have elevated titers of autoantibodies to TS-HDS or FFR3 as measured in
             Dr Alan Pestronk's lab at Washington University in St Louis.

        Exclusion Criteria:

          1. Any other known cause for small fiber neuropathy other than the presence of the
             elevated titers of auto-antibodies. For example patients with diabetes, HIV, Sjogrens,
             Vitamin deficiency etc.

          2. Patients with generalized, severe musculoskeletal conditions other than SFN that
             prevent a sufficient assessment of the patient by the physician

          3. Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant
             cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease).

          4. Severe liver disease (ALAT 3x > normal value).

          5. Severe kidney disease (creatinine 1.5x > normal value).

          6. Known hepatitis B, hepatitis C or HIV infection.

          7. Patients with a history of deep vein thrombosis (DVT) within the last year prior to
             baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or
             deep vein thrombosis.

          8. Body mass index (BMI) ≥40 kg/m2.

          9. Medical conditions whose symptoms and effects could alter protein catabolism and/or
             IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).

         10. Known IgA deficiency with antibodies to IgA.

         11. History of hypersensitivity, anaphylaxis or severe systemic response to
             immuno-globulin, blood or plasma derived products, or any component of Gamunex.

         12. Known blood hyperviscosity, or other hypercoagulable states.

         13. Use of IgG products within six months prior to enrolment.

         14. Use of other blood or plasma-derived products within three months prior to enrollment.

         15. Patients with a history of drug or alcohol abuse within the past five years prior to
             enrollment.

         16. Patients unable or unwilling to understand or comply with the study protocol

         17. Participating in another interventional clinical study with investigational treatment
             within three months prior to enrollment.

         18. Women who are breast feeding, pregnant, or planning to become pregnant, or are
             unwilling to use an effective birth control method (such as implants, injectable,
             combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or
             vasectomized partner) while on study.