Small Fiber NeuropathyPhase 2NCT03401073

IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3

A Phase 2 study testing Intravenous immunoglobulin and 0.9% Sodium Chloride in people with Small Fiber Neuropathy and Idiopathic Peripheral Neuropathy, run by Beth Israel Deaconess Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Any age
Conditions the study is for: Small Fiber Neuropathy, Idiopathic Peripheral Neuropathy
What is being tested?: Intravenous immunoglobulin and 0.9% Sodium Chloride
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 1 Sep 2018to 1 Feb 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 18Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Beth Israel Deaconness Medical Center
Boston, Massachusetts, 02215

Other trials in United States

About this study

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

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.

Read the detailed description

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)

Conditions: Small Fiber Neuropathy, Idiopathic Peripheral Neuropathy
Being tested: Intravenous immunoglobulin, 0.9% Sodium Chloride
Keywords: small Fiber Neuropathy, Idiopathic Peripheral Neuropathy, IVIg, Gamunex-C
Medical subject headings: Small Fiber Neuropathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intravenous immunoglobulinDrug
Also called Gamunex-C Liquid
Gamunex-C [immune globulin injection (human) 10% caprylate/chromatography purified] is a sterile solution of human immune globulin protein.
0.9% Sodium ChlorideDrug
Also called Saline
Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.

Study groups in NCT03401073
Study group	Role	What they receive
0.9% Sodium Chloride	Placebo comparator	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. Receives: Drug: 0.9% Sodium Chloride
Intravenous Immunoglobulin	Experimental	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 Receives: Drug: Intravenous immunoglobulin

What is being measured

The primary outcome is the main question the study is designed to answer.

The Change in Nerve Fiber Density Between Visits 1 and 8.
Difference in intra-epidermal nerve fiber density between visits 1 and 8 will be measured.
Intra-epidermal nerve fiber density is a quantitative measure of the number of nerve fibers per millimeter. The outcome is the number of nerve fibers measured at visit 8 minus the number of nerve fibers measured at visit 1. A positive value indicates that nerve fiber density has increased (a better outcome), a negative value indicates that the nerve fiber density has decreased (a worse outcome).
Measured: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).

Secondary outcomes (2)

The Change in Neuropathic Pain Severity Between Visits 1 and 8.
The visual analog scale (VAS) of pain allows for quantification of neuropathic pain.
The VAS pain scale depicts a line ranging from 0 (no pain) to 10 (worst possible pain). The scale is ordinal ranging from 0-10.
The difference in pain between visit 1 and visit 8 (pain measured at visit 8 subtracted from the score at visit 1) is the range. Positive values indicate an increase in pain (worse outcome), negative values indicate an improvement in pain (better outcome).
Measured: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).
2) The Difference in Change Between Quantified Utah Early Neuropathy Examination Scores, Between Treatment and Placebo Groups Between Visits 1 and 8.
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.
The UENS scale ranges from 0 (no neuropathy) to 42 (severe small fiber neuropathy). The outcome measure is the UENS score from Visit 8 minus the UENS score at visit 1. The difference in the two scores indicates the change in neuropathy severity. A positive value indicates that neuropathy has worsened over the course of the study, a negative value indicates that neuropathy has improved over the course of the study.
Measured: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 20181 Feb 2022

First posted17 Jan 2018
Study start1 Sep 2018
Primary completion1 Feb 2022
Study completion1 Feb 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (15)Papers the sponsor has linked to this study.
Other trials for Small Fiber NeuropathyStudies of the same condition, open and under way.
More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03401073
Sponsor's protocol ID: 2017P000592
Status last verified: Aug 2023
First submitted: 10 Jan 2018
Last updated: 13 Sep 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Gibbons CH. Small fiber neuropathies. Continuum (Minneap Minn). 2014 Oct;20(5 Peripheral Nervous System Disorders):1398-412. doi: 10.1212/01.CON.0000455874.68556.02.
PubMed 25299289
Cortez M, Singleton JR, Smith AG. Glucose intolerance, metabolic syndrome, and neuropathy. Handb Clin Neurol. 2014;126:109-22. doi: 10.1016/B978-0-444-53480-4.00009-6.
PubMed 25410218
Peltier A, Goutman SA, Callaghan BC. Painful diabetic neuropathy. BMJ. 2014 May 6;348:g1799. doi: 10.1136/bmj.g1799.
PubMed 24803311
Kass-Iliyya L, Javed S, Gosal D, Kobylecki C, Marshall A, Petropoulos IN, Ponirakis G, Tavakoli M, Ferdousi M, Chaudhuri KR, Jeziorska M, Malik RA, Silverdale MA. Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study. Parkinsonism Relat Disord. 2015 Dec;21(12):1454-60. doi: 10.1016/j.parkreldis.2015.10.019. Epub 2015 Nov 3.
PubMed 26578039
Lefaucheur JP, Wahab A, Plante-Bordeneuve V, Sene D, Menard-Lefaucheur I, Rouie D, Tebbal D, Salhi H, Creange A, Zouari H, Ng Wing Tin S. Diagnosis of small fiber neuropathy: A comparative study of five neurophysiological tests. Neurophysiol Clin. 2015 Dec;45(6):445-55. doi: 10.1016/j.neucli.2015.09.012. Epub 2015 Nov 17.
PubMed 26596193
Kafaie J, Al Balushi A, Kim M, Pestronk A. Clinical and Laboratory Profiles of Idiopathic Small Fiber Neuropathy in Children: Case Series. J Clin Neuromuscul Dis. 2017 Sep;19(1):31-37. doi: 10.1097/CND.0000000000000178.
PubMed 28827487
Pestronk A, Schmidt RE, Choksi RM, Sommerville RB, Al-Lozi MT. Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS. Muscle Nerve. 2012 Jun;45(6):866-72. doi: 10.1002/mus.23256.
PubMed 22581541
Antoine JC, Boutahar N, Lassabliere F, Reynaud E, Ferraud K, Rogemond V, Paul S, Honnorat J, Camdessanche JP. Antifibroblast growth factor receptor 3 antibodies identify a subgroup of patients with sensory neuropathy. J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1347-55. doi: 10.1136/jnnp-2014-309730. Epub 2015 Jan 27.
PubMed 25628376
Hahn AF, Bolton CF, Zochodne D, Feasby TE. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, cross-over study. Brain. 1996 Aug;119 ( Pt 4):1067-77. doi: 10.1093/brain/119.4.1067.
PubMed 8813271
Mendell JR, Barohn RJ, Freimer ML, Kissel JT, King W, Nagaraja HN, Rice R, Campbell WW, Donofrio PD, Jackson CE, Lewis RA, Shy M, Simpson DM, Parry GJ, Rivner MH, Thornton CA, Bromberg MB, Tandan R, Harati Y, Giuliani MJ; Working Group on Peripheral Neuropathy. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 2001 Feb 27;56(4):445-9. doi: 10.1212/wnl.56.4.445.
PubMed 11222785
Cocito D, Ciaramitaro P, Isoardo G, Barbero P, Migliaretti G, Pipieri A, Proto G, Quadri R, Bergamasco B, Durelli L. Intravenous immunoglobulin as first treatment in diabetics with concomitant distal symmetric axonal polyneuropathy and CIDP. J Neurol. 2002 Jun;249(6):719-22. doi: 10.1007/s00415-002-0698-0.
PubMed 12111305
Eftimov F, Winer JB, Vermeulen M, de Haan R, van Schaik IN. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2013 Dec 30;(12):CD001797. doi: 10.1002/14651858.CD001797.pub3.
PubMed 24379104
Singleton JR, Bixby B, Russell JW, Feldman EL, Peltier A, Goldstein J, Howard J, Smith AG. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst. 2008 Sep;13(3):218-27. doi: 10.1111/j.1529-8027.2008.00180.x.
PubMed 18844788
Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, Nolano M, Merkies IS, Polydefkis M, Smith AG, Sommer C, Valls-Sole J; European Federation of Neurological Societies; Peripheral Nerve Society. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010 Jul;17(7):903-12, e44-9. doi: 10.1111/j.1468-1331.2010.03023.x.
PubMed 20642627
Nolano M, Biasiotta A, Lombardi R, Provitera V, Stancanelli A, Caporaso G, Santoro L, Merkies IS, Truini A, Porretta-Serapiglia C, Cazzato D, Dacci P, Vitale DF, Lauria G. Epidermal innervation morphometry by immunofluorescence and bright-field microscopy. J Peripher Nerv Syst. 2015 Dec;20(4):387-91. doi: 10.1111/jns.12146.
PubMed 26309146

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Enrolling by invitation
Pilot Study to Evaluate Changes in Intra-Epidermal Nerve Fiber Density (IENFD) in Patients With Small-Fiber Neuropathy
Small Fiber Neuropathy

All Small Fiber Neuropathy trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03401073
Acronym / sponsor ID: 2017P000592
Conditions: Small Fiber Neuropathy, Idiopathic Peripheral Neuropathy
Keywords: small Fiber Neuropathy, Idiopathic Peripheral Neuropathy, IVIg, Gamunex-C
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Beth Israel Deaconess Medical CenterUniversity, hospital or other
Collaborators: Phoenix Neurological Associates, LTD
Study start: 1 Sep 2018 (actual)
Primary completion: 1 Feb 2022 (actual)
Study completion: 1 Feb 2022 (actual)
First posted: 17 Jan 2018 (actual)
Results: Posted 13 Sep 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 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.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
0.9% Sodium Chloride	Placebo comparator	Drug: 0.9% Sodium ChlorideThe 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.
Intravenous Immunoglobulin	Experimental	Drug: Intravenous immunoglobulinThe 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

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (18 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intravenous immunoglobulinAlso: Gamunex-C LiquidGamunex-C [immune globulin injection (human) 10% caprylate/chromatography purified] is a sterile solution of human immune globulin protein.	Drug	Intravenous Immunoglobulin
0.9% Sodium ChlorideAlso: SalineSodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.	Drug	0.9% Sodium Chloride

Primary outcome

The Change in Nerve Fiber Density Between Visits 1 and 8.
Time frame: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).
Difference in intra-epidermal nerve fiber density between visits 1 and 8 will be measured. Intra-epidermal nerve fiber density is a quantitative measure of the number of nerve fibers per millimeter. The outcome is the number of nerve fibers measured at visit 8 minus the number of nerve fibers measured at visit 1. A positive value indicates that nerve fiber density has increased (a better outcome), a negative value indicates that the nerve fiber density has decreased (a worse outcome).

2 secondary outcomes

The Change in Neuropathic Pain Severity Between Visits 1 and 8.
Time frame: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).
2) The Difference in Change Between Quantified Utah Early Neuropathy Examination Scores, Between Treatment and Placebo Groups Between Visits 1 and 8.
Time frame: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).

Results and safety

Results posted to the registry on 13 Sep 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.9% Sodium Chloride	10	9
Intravenous Immunoglobulin	10	8

Primary outcome: The Change in Nerve Fiber Density Between Visits 1 and 8.

Time frame: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).. Mean (Standard Deviation). Unit: fibers/mm

Measure	0.9% Sodium Chloride n = 9	Intravenous Immunoglobulin n = 8
Value	0.5 (0.8)	0.6 (0.6)

Population analysed: The 17 study completers were analyzed as part of the final results.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
0.9% Sodium Chloride	0 of 10 (0%)	9 of 10 (90%)	0 of 10
Intravenous Immunoglobulin	0 of 10 (0%)	8 of 10 (80%)	0 of 10

Limitations and caveats (from the sponsor): This was a small pilot study that was underpowered to detect changes to secondary endpoints. There was a 15% dropout. Despite several publications that note an association between TS-HDS and FGFR-3 autoantibodies in neuropathy, we do not have evidence for pathogenicity (supported by a non-insignificant number of patients excluded from the study with autoantibodies but without evidence of neuropathy). This too may have limited the potential treatment effect of immune globulin.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25299289Gibbons CH. Small fiber neuropathies. Continuum (Minneap Minn). 2014 Oct;20(5 Peripheral Nervous System Disorders):1398-412. doi: 10.1212/01.CON.0000455874.68556.02.
Background: PubMed 25410218Cortez M, Singleton JR, Smith AG. Glucose intolerance, metabolic syndrome, and neuropathy. Handb Clin Neurol. 2014;126:109-22. doi: 10.1016/B978-0-444-53480-4.00009-6.
Background: PubMed 24803311Peltier A, Goutman SA, Callaghan BC. Painful diabetic neuropathy. BMJ. 2014 May 6;348:g1799. doi: 10.1136/bmj.g1799.
Background: PubMed 26578039Kass-Iliyya L, Javed S, Gosal D, Kobylecki C, Marshall A, Petropoulos IN, Ponirakis G, Tavakoli M, Ferdousi M, Chaudhuri KR, Jeziorska M, Malik RA, Silverdale MA. Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study. Parkinsonism Relat Disord. 2015 Dec;21(12):1454-60. doi: 10.1016/j.parkreldis.2015.10.019. Epub 2015 Nov 3.
Background: PubMed 26596193Lefaucheur JP, Wahab A, Plante-Bordeneuve V, Sene D, Menard-Lefaucheur I, Rouie D, Tebbal D, Salhi H, Creange A, Zouari H, Ng Wing Tin S. Diagnosis of small fiber neuropathy: A comparative study of five neurophysiological tests. Neurophysiol Clin. 2015 Dec;45(6):445-55. doi: 10.1016/j.neucli.2015.09.012. Epub 2015 Nov 17.
Background: PubMed 28827487Kafaie J, Al Balushi A, Kim M, Pestronk A. Clinical and Laboratory Profiles of Idiopathic Small Fiber Neuropathy in Children: Case Series. J Clin Neuromuscul Dis. 2017 Sep;19(1):31-37. doi: 10.1097/CND.0000000000000178.
Background: PubMed 22581541Pestronk A, Schmidt RE, Choksi RM, Sommerville RB, Al-Lozi MT. Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS. Muscle Nerve. 2012 Jun;45(6):866-72. doi: 10.1002/mus.23256.
Background: PubMed 25628376Antoine JC, Boutahar N, Lassabliere F, Reynaud E, Ferraud K, Rogemond V, Paul S, Honnorat J, Camdessanche JP. Antifibroblast growth factor receptor 3 antibodies identify a subgroup of patients with sensory neuropathy. J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1347-55. doi: 10.1136/jnnp-2014-309730. Epub 2015 Jan 27.
Background: PubMed 8813271Hahn AF, Bolton CF, Zochodne D, Feasby TE. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, cross-over study. Brain. 1996 Aug;119 ( Pt 4):1067-77. doi: 10.1093/brain/119.4.1067.
Background: PubMed 11222785Mendell JR, Barohn RJ, Freimer ML, Kissel JT, King W, Nagaraja HN, Rice R, Campbell WW, Donofrio PD, Jackson CE, Lewis RA, Shy M, Simpson DM, Parry GJ, Rivner MH, Thornton CA, Bromberg MB, Tandan R, Harati Y, Giuliani MJ; Working Group on Peripheral Neuropathy. Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 2001 Feb 27;56(4):445-9. doi: 10.1212/wnl.56.4.445.
Background: PubMed 12111305Cocito D, Ciaramitaro P, Isoardo G, Barbero P, Migliaretti G, Pipieri A, Proto G, Quadri R, Bergamasco B, Durelli L. Intravenous immunoglobulin as first treatment in diabetics with concomitant distal symmetric axonal polyneuropathy and CIDP. J Neurol. 2002 Jun;249(6):719-22. doi: 10.1007/s00415-002-0698-0.
Background: PubMed 24379104Eftimov F, Winer JB, Vermeulen M, de Haan R, van Schaik IN. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2013 Dec 30;(12):CD001797. doi: 10.1002/14651858.CD001797.pub3.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christopher Gibbons, MD principal investigator

Beth Israel Deaconess Medical Cednter

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Change in Nerve Fiber Density Between Visits 1 and 8. (time frame: Visit 1 (time zero) and visit 8 (range of visit time 22-27 weeks after visit 1), thus a total of 22-27 weeks for the study (the range is provided to ensure final follow up is completed despite any conflicts with travel or holidays).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03401073, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.