Phase 2
N=20
IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3
Small Fiber Neuropathy · Idiopathic Peripheral Neuropathy
Bottom Line
View on ClinicalTrials.gov: NCT03401073 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
Sep 2023
Primary outcome: Primary: The Change in Nerve Fiber Density Between Visits 1 and 8. — 0.5; 0.6 fibers/mm
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Intravenous immunoglobulin (Drug); 0.9% Sodium Chloride (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Beth Israel Deaconess Medical Center
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Change in Nerve Fiber Density Between Visits 1 and 8. |
0.5; 0.6 | — |
| SECONDARY The Change in Neuropathic Pain Severity Between Visits 1 and 8. |
-1.7; -1.9 | — |
| SECONDARY 2) The Difference in Change Between Quantified Utah Early Neuropathy Examination Scores, Between Treatment and Placebo Groups Between Visits 1 and 8. |
-3.0; -1.8 | — |
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
- 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.
- Patients must have a baseline pain score on a VAS scale of Greater or equal to 4/10
- 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
- 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.
- Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician
- Cardiac insufficiency (New York Heart Association III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease).
- Severe liver disease (ALAT 3x > normal value).
- Severe kidney disease (creatinine 1.5x > normal value).
- Known hepatitis B, hepatitis C or HIV infection.
- 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.
- Body mass index (BMI) ≥40 kg/m2.
- Medical conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
- Known IgA deficiency with antibodies to IgA.
- History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of Gamunex.
- Known blood hyperviscosity, or other hypercoagulable states.
- Use of IgG products within six months prior to enrolment.
- Use of other blood or plasma-derived products within three months prior to enrollment.
- Patients with a history of drug or alcohol abuse within the past five years prior to enrollment.
- Patients unable or unwilling to understand or comply with the study protocol
- Participating in another interventional clinical study with investigational treatment within three months prior to enrollment.
- 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.
Data sourced from ClinicalTrials.gov (NCT03401073). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.