Trial Outcomes & Findings for Mechanisms of Glucose Lowering Effect of Colesevelam HCl (NCT NCT00596427)
NCT ID: NCT00596427
Last Updated: 2012-10-12
Results Overview
Changes from baseline of fasting EGP after 12 weeks of placebo or colesevelam treatment.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
60 participants
Primary outcome timeframe
baseline and 12 weeks
Results posted on
2012-10-12
Participant Flow
Participants with type 2 diabetes. All pre-existing drug treatments were stable for at least 3 months prior.
Participants excluded based on fasting plasma glucose levels, fasting serum triglyceride levels, LDL-cholesterol levels, pregnancy or a history of liver, biliary, or intestinal diseases. Participants treated with insulin or lipid agent less than six months prior were excluded as well.
Participant milestones
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
Subjects received six tablets a day of matched placebo(3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
30
|
|
Overall Study
COMPLETED
|
26
|
28
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
Reasons for withdrawal
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
Subjects received six tablets a day of matched placebo(3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
|
Overall Study
Increased Fasting Triacylglycerol level
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Mechanisms of Glucose Lowering Effect of Colesevelam HCl
Baseline characteristics by cohort
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=30 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=30 Participants
Subjects received six tablets a day of matched placebo(3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
49 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Age Continuous
|
59 years
STANDARD_DEVIATION 9 • n=93 Participants
|
56 years
STANDARD_DEVIATION 9 • n=4 Participants
|
57.5 years
STANDARD_DEVIATION 9 • n=27 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=93 Participants
|
30 participants
n=4 Participants
|
60 participants
n=27 Participants
|
|
BMI
|
30 kg/m2
STANDARD_DEVIATION 5 • n=93 Participants
|
31 kg/m2
STANDARD_DEVIATION 5 • n=4 Participants
|
30.5 kg/m2
STANDARD_DEVIATION 5 • n=27 Participants
|
|
Weight
|
84 kg
STANDARD_DEVIATION 16 • n=93 Participants
|
88 kg
STANDARD_DEVIATION 19 • n=4 Participants
|
86 kg
STANDARD_DEVIATION 18 • n=27 Participants
|
|
HbA 1c
|
8.5 percentage
STANDARD_DEVIATION 1.2 • n=93 Participants
|
8.0 percentage
STANDARD_DEVIATION 0.9 • n=4 Participants
|
8.25 percentage
STANDARD_DEVIATION 1.05 • n=27 Participants
|
|
Glucose
|
9.2 mmol/l
STANDARD_DEVIATION 2.3 • n=93 Participants
|
8.4 mmol/l
STANDARD_DEVIATION 2.4 • n=4 Participants
|
8.8 mmol/l
STANDARD_DEVIATION 2.3 • n=27 Participants
|
|
Insulin
|
76 pmol/l
STANDARD_DEVIATION 42 • n=93 Participants
|
97 pmol/l
STANDARD_DEVIATION 42 • n=4 Participants
|
87 pmol/l
STANDARD_DEVIATION 42 • n=27 Participants
|
|
Total cholesterol
|
4.6 mmol/l
STANDARD_DEVIATION 1.2 • n=93 Participants
|
4.6 mmol/l
STANDARD_DEVIATION 1.3 • n=4 Participants
|
4.6 mmol/l
STANDARD_DEVIATION 1.3 • n=27 Participants
|
|
LDL-cholesterol
|
2.8 mmol/l
STANDARD_DEVIATION 0.8 • n=93 Participants
|
2.8 mmol/l
STANDARD_DEVIATION 1.0 • n=4 Participants
|
2.8 mmol/l
STANDARD_DEVIATION 0.9 • n=27 Participants
|
|
HDL-cholesterol
|
0.9 mmol/l
STANDARD_DEVIATION 0.2 • n=93 Participants
|
1.0 mmol/l
STANDARD_DEVIATION 0.2 • n=4 Participants
|
1.0 mmol/l
STANDARD_DEVIATION 0.2 • n=27 Participants
|
|
Triacylglycerol
|
2.2 mmol/l
STANDARD_DEVIATION 0.8 • n=93 Participants
|
2.0 mmol/l
STANDARD_DEVIATION 0.9 • n=4 Participants
|
2.1 mmol/l
STANDARD_DEVIATION 0.9 • n=27 Participants
|
PRIMARY outcome
Timeframe: baseline and 12 weeksChanges from baseline of fasting EGP after 12 weeks of placebo or colesevelam treatment.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=27 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Fasting Endogenous Glucose Production (EGP)
|
0.19 umol per kg Fat-Free Mass (FFM) per min
Standard Error 0.78
|
1.59 umol per kg Fat-Free Mass (FFM) per min
Standard Error 0.77
|
PRIMARY outcome
Timeframe: baseline and 12 weeksChange from baseline of fasting gluconeogenesis after 12 weeks of placebo or colesevelam treatment.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=26 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Fasting Gluconeogenesis
|
0.02 micromoles (µmol) per kg FFM per min
Standard Error 0.32
|
-0.19 micromoles (µmol) per kg FFM per min
Standard Error 0.27
|
PRIMARY outcome
Timeframe: baseline and 12 weeksChange from baseline of fasting glycogenolysis after 12 weeks of placebo or colesevelam treatment.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=25 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Fasting Glycogenolysis
|
0.11 µmol per kilograms (kg) FFM per min
Standard Error 0.81
|
1.78 µmol per kilograms (kg) FFM per min
Standard Error 0.69
|
PRIMARY outcome
Timeframe: baseline and 12 weeksChange from baseline of the rate of appearance of oral glucose after 12 weeks of placebo or colesevelam treatment. Mean of values obtained between 0 and 300 min is reported.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=25 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=26 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Rate of Appearance of Exogenous Glucose (Glucose Absorption)
|
0 µmol per kg FFM per minute (min)
Standard Error 0.56
|
1 µmol per kg FFM per minute (min)
Standard Error 0.63
|
SECONDARY outcome
Timeframe: baseline and 12 weeksChanges from baseline of total GLP-1 AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Total Glucagon-like Peptide (GLP-1) Area Under the Curve (AUC)
|
5 picomoles (pmol)/Liter (L) x minute (min
Standard Deviation 2
|
-3 picomoles (pmol)/Liter (L) x minute (min
Standard Deviation 1
|
SECONDARY outcome
Timeframe: baseline and 12 weeksChanges from baseline of total GIP-1 AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Total Glucose-dependent Insulinotropic Polypeptide (GIP) AUC
|
7 pmol/l x min
Standard Deviation 2
|
-6 pmol/l x min
Standard Deviation 2
|
SECONDARY outcome
Timeframe: baseline and 12 weeksChanges from baseline in fasting fractional DNL after 12 weeks of colesevelam or placebo treatment were calculated. Fractional DNL represents the fraction of palmitate in very-low density lipoproteins-triglycerides (VLDL-TG) that was newly synthesized.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=26 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Fasting Fractional De Novo Lipogenesis (DNL)
|
-0.6 percent new palmitate
Standard Error 0.57
|
-1.4 percent new palmitate
Standard Error 0.58
|
SECONDARY outcome
Timeframe: baseline and 12 weeksChanges from baseline in fasting fractional cholesterol synthesis after 12 weeks of colesevelam or placebo treatment. Fractional Cholesterol synthesis represents the fraction of free cholesterol in plasma that was newly synthesised.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Fasting Fractional Cholesterol Synthesis
|
3.0 Percent new cholesterol
Standard Error 0.4
|
0.5 Percent new cholesterol
Standard Error 0.4
|
SECONDARY outcome
Timeframe: baseline and 12 weeksChanges from baseline in fractional cholic acid synthesis after 12 weeks of colesevelam or placebo treatment were evaluated. Fractional cholic acid synthesis represents the relative amount of cholic acid that is made from newly synthesised cholesterol.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Postprandial Fractional Cholic Acid Synthesis
|
5.5 Percent new cholic acid
Standard Error 1.0
|
1.7 Percent new cholic acid
Standard Error 1.0
|
SECONDARY outcome
Timeframe: baseline and 12 weeksChanges from baseline of glucagon AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Glucagon AUC
|
4 picograms (pg)/milliter (ml) x min
Standard Error 3
|
-4 picograms (pg)/milliter (ml) x min
Standard Error 4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 12 weeksChanges from baseline of HbA1c after 12 weeks of placebo or colesevelam treatment.
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Glycosylated Hemoglobin (HbAlc)
|
-0.3 percentage
Standard Deviation 0.2
|
0.3 percentage
Standard Deviation 0.2
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 12 weeksChanges from baseline of glucose AUC after 12 weeks of placebo or colesevelam treatment. AUC values were calculated by the trapezoid method using all results between 0 and 300 minutes
Outcome measures
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 Participants
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 Participants
Subjects received six tablets a day of colesevelam matched placebo for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Glucose AUC
|
-0.8 millimoles (mmol)/l x min
Standard Deviation 0.4
|
0.5 millimoles (mmol)/l x min
Standard Deviation 0.4
|
Adverse Events
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
Type-2 Diabetes Mellitus Patients Treated With Placebo
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Type-2 Diabetes Mellitus Patients Treated With Colesevelam
n=26 participants at risk；n=30 participants at risk
Subjects received six tablets a day of colesevelam (3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
Type-2 Diabetes Mellitus Patients Treated With Placebo
n=28 participants at risk；n=30 participants at risk
Subjects received six tablets a day of matched placebo(3.75g/day) for 12 weeks; three tablets with lunch and three tablets with dinner.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal cramps
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
Gastrointestinal disorders
Constipation
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
3.6%
1/28 • Number of events 1 • 12 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/26 • 12 weeks
|
17.9%
5/28 • Number of events 5 • 12 weeks
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/26 • 12 weeks
|
7.1%
2/28 • Number of events 2 • 12 weeks
|
|
Gastrointestinal disorders
Nausea
|
11.5%
3/26 • Number of events 3 • 12 weeks
|
17.9%
5/28 • Number of events 5 • 12 weeks
|
|
Nervous system disorders
Headache
|
15.4%
4/26 • Number of events 4 • 12 weeks
|
17.9%
5/28 • Number of events 5 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
2/26 • Number of events 2 • 12 weeks
|
3.6%
1/28 • Number of events 1 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/26 • 12 weeks
|
7.1%
2/28 • Number of events 2 • 12 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chest congestion
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/26 • 12 weeks
|
3.6%
1/28 • Number of events 1 • 12 weeks
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/26 • 12 weeks
|
3.6%
1/28 • Number of events 1 • 12 weeks
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
General disorders
Edema peripheral
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
General disorders
Dry mouth
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
Musculoskeletal and connective tissue disorders
Lethargic
|
7.7%
2/26 • Number of events 2 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
Vascular disorders
Rapid pulse
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
|
Vascular disorders
Chest pain
|
3.8%
1/26 • Number of events 1 • 12 weeks
|
0.00%
0/28 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place