Trial Outcomes & Findings for The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes (NCT NCT02915263)

NCT ID: NCT02915263

Last Updated: 2024-05-07

Results Overview

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 7 weeks (final evaluation) minus the UENS score from the baseline visit. A positive value indicates that neuropathy worsened over the course of the trial (a worse outcome), a negative score indicates that neuropathy improved over the course of the trial (a better outcome).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

7 weeks after first infusion.

Results posted on

2024-05-07

Participant Flow

Participant milestones

Participant milestones
Measure
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Overall Study
STARTED
6
7
Overall Study
COMPLETED
3
5
Overall Study
NOT COMPLETED
3
2

Reasons for withdrawal

Reasons for withdrawal
Measure
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Overall Study
Covid
3
2

Baseline Characteristics

The Efficacy Of Intravenous Immunoglobulin Therapy In Treatment Induced Neuropathy Of Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
0.9% Sodium Chloride
n=6 Participants
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
n=7 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Total
n=13 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
6 Participants
n=5 Participants
7 Participants
n=7 Participants
13 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Continuous
41 years
STANDARD_DEVIATION 12.5 • n=5 Participants
39 years
STANDARD_DEVIATION 13.3 • n=7 Participants
40 years
STANDARD_DEVIATION 12.9 • n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
4 Participants
n=7 Participants
8 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
6 Participants
n=5 Participants
7 Participants
n=7 Participants
13 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
6 participants
n=5 Participants
7 participants
n=7 Participants
13 participants
n=5 Participants

PRIMARY outcome

Timeframe: 7 weeks after first infusion.

Population: A total of 3 participants completed treatment with placebo and 4 with IVIG. The remaining participants were unable to continue due to COVID 19 pandemic shutdown of all research activities. Funding was withdrawn at that time and no further studies were completed.

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 7 weeks (final evaluation) minus the UENS score from the baseline visit. A positive value indicates that neuropathy worsened over the course of the trial (a worse outcome), a negative score indicates that neuropathy improved over the course of the trial (a better outcome).

Outcome measures

Outcome measures
Measure
0.9% Sodium Chloride
n=3 Participants
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
n=4 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Change in Sensory Neuropathy as Measured by the Utah Early Neuropathy Score (UENS).
-1.5 units on a scale
Standard Deviation 10.7
-3.9 units on a scale
Standard Deviation 12.4

PRIMARY outcome

Timeframe: 7 weeks after first infusion

The visual analog scale (VAS) of pain allows for quantification of neuropathic pain. The VAS pain scale is a line with markings that range from 0 (no pain) to 10 (worse pain), with whole digit intervals (thus an 11 point scale). This outcome measure is the VAS pain score at the final visit (7 weeks after first infusion) minus the VAS pain score at the baseline visit. A positive result indicates that pain increased over the course of the study (a worse outcome), a negative result indicates that pain improved over the course of the trial (a better outcome).

Outcome measures

Outcome measures
Measure
0.9% Sodium Chloride
n=3 Participants
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
n=4 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Change in Neuropathic Pain Severity as Measured by the Pain Visual Analogue Scores (VAS).
-1.1 units on a scale
Standard Deviation 2.2
-1.6 units on a scale
Standard Deviation 2.4

SECONDARY outcome

Timeframe: 7 weeks after first infusion

Population: The change in nerve fiber density.

Skin biopsies will be evaluated by measuring the Intra-epidermal nerve fiber density. Nerve fiber density is measured in the number of nerve fibers per millimeter. This outcome measure is the nerve fiber density at the final visit (7 weeks after the initial infusion) minus the nerve fiber density from the baseline visit. A positive result indicates that nerve fiber density increased over the course of the study (a better outcome), a negative result indicates that nerve fiber density decreased over the course of the trial (a worse outcome).

Outcome measures

Outcome measures
Measure
0.9% Sodium Chloride
n=3 Participants
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
n=4 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Change in Neuropathy Severity as Measured by Skin Biopsies.
-0.6 fibers/mm
Standard Deviation 2.5
-0.3 fibers/mm
Standard Deviation 2.3

SECONDARY outcome

Timeframe: 7 weeks after first infusion

Population: A change in the heart rate variability during paced breathing.

The standardized autonomic nervous system testing evaluates the heart rate variability to paced breathing. Heart rate variability is reported in beats per minutes. The outcome measure is the heart rate variability at the final visit (7 weeks after initial infusion) minus the heart rate variability of the baseline visit. A positive result indicates an increase in heart rate variability (a better outcome), a negative result indicates a decrease in heart rate variability (a worse outcome).

Outcome measures

Outcome measures
Measure
0.9% Sodium Chloride
n=3 Participants
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
n=4 Participants
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
Change in Autonomic Neuropathy as Measured by Standardized Autonomic Nervous System Testing.
2.1 beats/minute
Standard Deviation 3.2
2.5 beats/minute
Standard Deviation 3.4

Adverse Events

0.9% Sodium Chloride

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

IGIV-C

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
0.9% Sodium Chloride
n=3 participants at risk
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 5 days. 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. 0.9% Sodium Chloride: Sodium Chloride (also known as saline) is a solution of sodium chloride, or salt, and sterile water.
IGIV-C
n=4 participants at risk
The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The treatment will consist of IVIG administered at 2 grams/kg divided over 5 days, with a follow up treatment 3 weeks (+/-3 days) later of IVIG 1gram/kg administered over 2 day (or placebo). IGIV-C: Gamunex-C \[immune globulin injection (human) 10% caprylate/chromatography purified\] is a sterile solution of human immune globulin protein.
General disorders
Infusion reactions
33.3%
1/3 • Number of events 1 • 2 months
Adverse events recorded at the time of infusion, during interim visits and on phone screens between visits.
50.0%
2/4 • Number of events 2 • 2 months
Adverse events recorded at the time of infusion, during interim visits and on phone screens between visits.

Additional Information

Christopher Gibbons MD

Beth Israel Deaconess Medical Center

Phone: 617-632-8454

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place