IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3
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|ClinicalTrials.gov Identifier: NCT03401073|
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : December 7, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Small Fiber Neuropathy Idiopathic Peripheral Neuropathy||Drug: Intravenous immunoglobulin Drug: 0.9% Sodium Chloride||Phase 2|
Small fiber neuropathies, and mixed small and large fiber neuropathies, have many potential causes including diabetes, vitamin deficiencies, environmental and toxic exposures, HIV, autoimmune and paraproteinemias.
However, despite this broad differential at least 30% of cases of small fiber neuropathies remain idiopathic. There is therefore a growing interest in the potential for using IVIG in small fiber neuropathy without direct proof that the disorder is caused by immune reactions. We have recently uncovered two novel autoantibodies, TS-HDS and FGFR-3, that are targeted again peripheral neural structure. TS-HDS is a disaccharide component of glycosylation of heparin and heparin sulfate.
Patients with elevated levels of IgM against TS-HDS display clear small fiber loss with IgM deposits around the outside of medium- & larger-sized capillaries with C5b-9 complement deposits. FGFR-3 is a secreted cell surface receptor; genetic defects of FGFR-3 are linked to achrondroplasia and other bony abnormalities.
The antibodies to TS-HDS and FGFR-3 are detected in up to 20% of patients with otherwise idiopathic small fiber neuropathy, but are rare in patients without small fiber neuropathy.
Dr. Levine (a co-investigator on this project) recently presented 3 cases of small fiber associated with elevated levels of auto-antibodies to TS-HDS or FGFR-3 who were treated with IVIG at 2 gm/kg/month for 6 months. He examined skin biopsies for intra-epidermal nerve fiber density and patient self-reported pain scores at baseline and after six months of therapy. All 3 cases showed marked improvement in pain scores. The average reduction in pain was 54%. In addition there was a clear increase in the intra-epidermal nerve fiber density (IENFD) after 6 months of therapy. Pre-treatment IENFD was 1.6, 1.7, and 2.4 at the calf. After 6 months of therapy the IENFD was 8.4, 5.7, 3.3 respectively (these are clinically significant improvement in nerve fiber density.
The investigators believe these anecdotal cases suggest that TS-HDS and FGFR-3 antibodies may be a marker for a group of SFN patients that are immune mediated and may respond to IVIG. (This case series was presented as a poster at the American Academy of Neurology meeting in 2017)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Double-Blind, Placebo Controlled Trial of Intravenous Immunoglobulin Therapy in Patient With Small Fiber Neuropathy Associated With Autoantibodies to TS-HDS and FGFR3|
|Actual Study Start Date :||September 1, 2018|
|Estimated Primary Completion Date :||June 1, 2020|
|Estimated Study Completion Date :||June 1, 2020|
Placebo Comparator: 0.9% Sodium Chloride
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 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. 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
Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
Other Name: Saline
Experimental: Intravenous Immunoglobulin
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments
Drug: Intravenous immunoglobulin
Gamunex-C [immune globulin injection (human) 10% caprylate/chromatography purified] is a sterile solution of human immune globulin protein.
Other Name: Gamunex-C Liquid
- The change in nerve fiber density between visits 1 and 8. [ Time Frame: 22-27 weeks after screening visit ]Difference in intra-epidermal nerve fiber density between visits 1 and 8 will be measured
- The change in neuropathic pain severity between visits 1 and 8. [ Time Frame: 22-27 weeks after screening visit ]The visual analog scale (VAS) of pain allows for quantification of neuropathic pain (line from 0: no pain to 10:worst pain)
- 2) The difference in change between quantified Utah Early Neuropathy examination scores, between treatment and placebo groups between visits 1 and 8. [ Time Frame: 22-27 weeks after screening visit ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401073
|Contact: Sharika Rajan, MDfirstname.lastname@example.org|
|United States, Massachusetts|
|Beth Israel Deaconness Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: sharika rajan 617-632-8964 email@example.com|
|Principal Investigator: Christopher Gibbons, MD|
|Principal Investigator:||Christopher Gibbons, MD||Beth Israel Deaconess Medical Cednter|