A Phase 2 interventional study of Intravenous immunoglobulin and 0.9% Sodium Chloride in Small Fiber Neuropathy and Idiopathic Peripheral Neuropathy, sponsored by Beth Israel Deaconess Medical Center. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2023-09-13.
Sponsored by Beth Israel Deaconess Medical Center · Phase 2, Interventional, and Treatment
Among 12 studies in Small Fiber Neuropathy with a site in United States — 3 open to participants now, 3 under way, none of them phase 3. Small Fiber Neuropathy · United States.
Among the 12 studies in Small Fiber Neuropathy with a site in United States, this one is the 7th largest by enrollment of the 11 interventional ones that give a count, is the only one that started in 2018, is one of 6 in phase 2, and was the 6th registered.
50 studies on the registry are indexed under Small Fiber Neuropathy; 12 are open to participants now.
Browse Small Fiber Neuropathy studies →3 of the 12 studies in Small Fiber Neuropathy with a site in United States are open now. Recruiting first, the newest first:
Endeavor Health · Sites in United States
Ages 18+
Brigham and Women's Hospital · Sites in United States
Ages 18+
TriCity Research Center · Sites in United States
Ages 19+
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 9 Small Fiber Neuropathy studies recruiting now, 6 set no upper age limit and 2 stop at 75 or younger; none take children under 18; none take healthy volunteers.
This study: all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
12 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 1 · Phase 2 7
First in 2011; this study’s year is marked. 1 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 20 is below the median of 31 across 31 interventional studies indexed under Small Fiber Neuropathy.
Median enrollment 27 across the 11 interventional studies, 400 across the 1 observational. Of the 5 that completed or were terminated, 5 (100%) have results posted.
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3 of 12 have an industry lead sponsor. The 10 most frequent:
Beth Israel Deaconess Medical Center is the lead sponsor of 568 studies on the registry; 79 are open to participants now.
Of its 76 completed or terminated interventional studies of FDA-regulated products, 62 (82%) have results posted.
Beth Israel Deaconess Medical Center has 1 study filed under Small Fiber Neuropathy — fewer than ten, so there is no comparison to draw.
3 of the studies in Small Fiber Neuropathy with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04759443Brigham and Women's HospitalDetection of Small Fiber Neuropathy Using Skin Properties | 2027-02-01 |
| NCT04153422Endeavor HealthIVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies | 2027-08-27 |
| NCT07704931TriCity Research CenterPilot Study to Evaluate Changes in Intra-Epidermal Nerve Fiber Density (IENFD) in Patients With Small-Fiber Neuropathy | 2027-09-30 |
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Among the 12 studies in Small Fiber Neuropathy with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
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)
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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.
Also known as: Gamunex-C Liquid
Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
Also known as: Saline
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).
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).
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).
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.
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.
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).
Potential research subjects were recruited from Beth Israel Deaconess Medical Center (BIDMC) (Boston, MA) and HonorHealth Neurology (Phoenix, AZ). All recruited subjects signed a consent form approved by the Institutional Review Boards of BIDMC and HonorHealth.
| Milestone | 0.9% Sodium Chloride | Intravenous Immunoglobulin |
|---|---|---|
| Started | 10 | 10 |
| Completed | 9 | 8 |
| Not completed | 1 | 2 |
| Withdrew: Lost to follow-up | 1 | 2 |
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).
| fibers/mm | 0.9% Sodium Chloride | Intravenous Immunoglobulin |
|---|---|---|
| The Change in Nerve Fiber Density Between Visits 1 and 8. | 0.5 ± 0.8 | 0.6 ± 0.6 |
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).
| units on a scale | 0.9% Sodium Chloride | Intravenous Immunoglobulin |
|---|---|---|
| The Change in Neuropathic Pain Severity Between Visits 1 and 8. | -1.7 ± 0.9 | -1.9 ± 2.6 |
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.
| units on a scale | 0.9% Sodium Chloride | Intravenous Immunoglobulin |
|---|---|---|
| 2) The Difference in Change Between Quantified Utah Early Neuropathy Examination Scores, Between Treatment and Placebo Groups Between Visits 1 and 8. | -3.0 ± 5.8 | -1.8 ± 3.9 |
Collected over 6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 0.9% Sodium Chloride | 0/10 (0%) | 0/10 (0%) | 9/10 (90%) |
| Intravenous Immunoglobulin | 0/10 (0%) | 0/10 (0%) | 8/10 (80%) |
| Event | 0.9% Sodium Chloride | Intravenous Immunoglobulin |
|---|---|---|
| Infusion reactionProduct Issues | 9/10 | 8/10 |
| Age, Categorical(Participants) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 9 | 10 | 19 |
| >=65 years | 1 | 0 | 1 |
| Age, Continuous(Years) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| Mean | 51.3 ± 9.4 | 51.5 ± 7.8 | 51.4 ± 8.4 |
| Sex: Female, Male(Participants) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| Female | 5 | 6 | 11 |
| Male | 5 | 4 | 9 |
| Ethnicity (NIH/OMB)(Participants) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 2 | 3 |
| Not Hispanic or Latino | 9 | 8 | 17 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 9 | 9 | 18 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| United States | 10 | 10 | 20 |
| Intra-epidermal nerve fiber density(Fibers/mm) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| Mean | 2.02 ± 1.49 | 2.47 ± 1.83 | 2.25 ± 1.66 |
| Pain score(units on a scale) | 0.9% Sodium Chloride | Intravenous Immunoglobulin | Total |
|---|---|---|---|
| Mean | 5.5 ± 1.2 | 6.9 ± 1.8 | 6.2 ± 1.6 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Sep 2018 to primary completion in Feb 2022, 41 months.
Results were first posted in Sep 2023, 1 year 7 months after primary completion.
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Studies of the drug tested here: Immunoglobulins, Intravenous
Beth Israel Deaconess Medical Center →