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Trial Outcomes & Findings for Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes (NCT NCT02372253)

NCT ID: NCT02372253

Last Updated: 2020-02-05

Results Overview

Functional Beta Cell Mass as determined by the area under the curve (AUC) from a 2-hour Mixed Meal-Stimulated C-peptide after daily verapamil for 12 months. A greater improvement in insulin production (as an indirect measure of beta cell mass) in subjects receiving verapamil as compared to those receiving placebo would provide an indication of the efficacy of this intervention. The C-peptide AUC (0-120 min) was calculated by using the trapezoidal rule and was divided by the time of the test to obtain the mean AUC (in nmol/L).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

12 months

Results posted on

2020-02-05

Participant Flow

32 subjects with recent-onset Type 1 diabetes were screened for autoantibodies and MMTT-stimulated C-peptide. Five were not eligible for randomization (3 were antibody negative and 2 were C-peptide negative). One additional participant declined.

Participant milestones

Participant milestones
Measure
Verapamil
Verapamil Sustained Release (SR) 360mg Daily
Placebo
Matching Placebo
Overall Study
STARTED
13
13
Overall Study
COMPLETED
11
13
Overall Study
NOT COMPLETED
2
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Verapamil
Verapamil Sustained Release (SR) 360mg Daily
Placebo
Matching Placebo
Overall Study
Non Compliance
2
0

Baseline Characteristics

Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
Total
n=24 Participants
Total of all reporting groups
Age, Continuous
32.3 years
STANDARD_DEVIATION 2.3 • n=5 Participants
28.3 years
STANDARD_DEVIATION 2.1 • n=7 Participants
30.3 years
STANDARD_DEVIATION 2.2 • n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
5 Participants
n=7 Participants
10 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
8 Participants
n=7 Participants
14 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
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
White
10 Participants
n=5 Participants
13 Participants
n=7 Participants
23 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
11 participants
n=5 Participants
13 participants
n=7 Participants
24 participants
n=5 Participants
Body Mass Index
24.4 kg/m^2
STANDARD_DEVIATION 0.8 • n=5 Participants
22.1 kg/m^2
STANDARD_DEVIATION 0.7 • n=7 Participants
23.25 kg/m^2
STANDARD_DEVIATION 0.75 • n=5 Participants
Fasting Plasma Glucose
6.4 mmol/L
STANDARD_DEVIATION 1 • n=5 Participants
6.9 mmol/L
STANDARD_DEVIATION 1 • n=7 Participants
6.65 mmol/L
STANDARD_DEVIATION 1 • n=5 Participants
HbA1C
6.6 %
STANDARD_DEVIATION 0.4 • n=5 Participants
6.8 %
STANDARD_DEVIATION 0.3 • n=7 Participants
6.7 %
STANDARD_DEVIATION 0.4 • n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Functional Beta Cell Mass as determined by the area under the curve (AUC) from a 2-hour Mixed Meal-Stimulated C-peptide after daily verapamil for 12 months. A greater improvement in insulin production (as an indirect measure of beta cell mass) in subjects receiving verapamil as compared to those receiving placebo would provide an indication of the efficacy of this intervention. The C-peptide AUC (0-120 min) was calculated by using the trapezoidal rule and was divided by the time of the test to obtain the mean AUC (in nmol/L).

Outcome measures

Outcome measures
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
Functional Beta Cell Mass
0.74 nmol/L
Standard Error 0.07
0.46 nmol/L
Standard Error 0.08

SECONDARY outcome

Timeframe: 12 months

Percent change in exogenous insulin requirements over the last 7-14 consecutive days at 12 months. This will be assessed as a surrogate inverse marker of residual beta cell function.

Outcome measures

Outcome measures
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
Percent Change From Baseline in Exogenous Insulin Requirements
27.0 Percent Change
Standard Error 15.6
69.8 Percent Change
Standard Error 7.9

SECONDARY outcome

Timeframe: 12 weeks

Percent change in exogenous insulin requirements over the last 7-14 consecutive days at 12 weeks. This will be assessed as a surrogate inverse marker of residual beta cell function.

Outcome measures

Outcome measures
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
Percent Change From Baseline in Exogenous Insulin Requirements
5.9 Percent Change
Standard Error 11.4
26.0 Percent Change
Standard Error 9.5

SECONDARY outcome

Timeframe: 12 months

Glycemic control, as measured by HbA1c. In addition to being an important determinant of residual beta cell function/survival, it also helps reveal a more complete picture of beta cell function.

Outcome measures

Outcome measures
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
HbA1C
6.4 Percent
Standard Error 0.2
6.9 Percent
Standard Error 0.3

SECONDARY outcome

Timeframe: 12 weeks

Glycemic control, as measured by HbA1c. In addition to being an important determinant of residual beta cell function/survival, it also helps reveal a more complete picture of beta cell function.

Outcome measures

Outcome measures
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
HbA1c
6.0 Percent
Standard Error 0.1
6.6 Percent
Standard Error 0.3

SECONDARY outcome

Timeframe: 12 months

Glycemic control, as measured by hypoglycemic events.

Outcome measures

Outcome measures
Measure
Verapamil
n=11 Participants
Verapamil SR 360mg Daily
Placebo
n=13 Participants
Matching Placebo
Hypoglycemic Events
0.55 events per month
Standard Error 0.31
2.72 events per month
Standard Error 0.86

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks and 12 months

Beta cell markers. We will collect serum at baseline and at Week 12 and Months 6, 9 and 12 for future assessment of putative beta cell markers.

Outcome measures

Outcome data not reported

Adverse Events

Verapamil

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Placebo

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
Verapamil
n=11 participants at risk
Verapamil SR 360mg Daily
Placebo
n=13 participants at risk
Matching Placebo
Gastrointestinal disorders
Constipation
45.5%
5/11 • Number of events 5 • Adverse events were collected for the 1 year subjects received study treatment.
7.7%
1/13 • Number of events 1 • Adverse events were collected for the 1 year subjects received study treatment.
General disorders
Dizziness
9.1%
1/11 • Number of events 1 • Adverse events were collected for the 1 year subjects received study treatment.
0.00%
0/13 • Adverse events were collected for the 1 year subjects received study treatment.
General disorders
Nausea
9.1%
1/11 • Number of events 1 • Adverse events were collected for the 1 year subjects received study treatment.
0.00%
0/13 • Adverse events were collected for the 1 year subjects received study treatment.
General disorders
Headache
0.00%
0/11 • Adverse events were collected for the 1 year subjects received study treatment.
7.7%
1/13 • Number of events 1 • Adverse events were collected for the 1 year subjects received study treatment.

Additional Information

Anath Shalev, MD

UNIVERSITY OF ALABAMA AT BIRMINGHAM

Phone: 205-996-4777

Results disclosure agreements

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