Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to obtain continuous glucose monitoring (CGM) data from individuals taking Welchol compared to placebo. The CGM data will determine the effect on glucose control of adding Welchol to an anti-diabetic medication regimen.
Detailed description
To understand the effect of the addition of colesevelam HCl to oral agent therapy in individuals with type 2 diabetes on glycemic control by utilizing a novel technology, continuous glucose monitoring with ambulatory glucose profile analysis. To date there are no studies of this compound that have employed continuous glucose monitoring (CGM) with ambulatory glucose profile (AGP) analysis to obtain data that will detail the diurnal glucose patterns associated with this therapy. We plan to employ CGM at critical points throughout the study. AGP analysis will enable rapid assessment of the clinical status of the subject. Using statistically stable estimates of hourly values represented by five percentile curves AGP depicts glucose exposure, variability and stability. Previously, we have used AGP analysis to characterize glucose perturbations in individuals ranging from normal glucose tolerance to overt type 2 diabetes.
Interventions
DRUGcolesevelam HCl
3.75 grams of colesevelam HCl (6 tablets)
DRUGplacebo
Sponsors
International Diabetes Center at Park Nicollet
Daiichi Sankyo
HealthPartners Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects ≥18 and ≤75 years of age * Clinical diagnosis of type 2 diabetes * Currently treated with metformin, a sulfonylurea, or combination metformin/sulfonylurea; stable dose for ≥3 months * HbA1c of 7.0-9.0% inclusive * If taking lipid lowering medications, stable dose for \>30 days
Exclusion criteria
* Taken oral or injected prednisone or cortisone medications in the previous 30 days. (Topical or inhaled steroids will not be considered excluded medications.) * Current use of insulin or TZD's, or incretins * LDL \<70 mg/dL * Serum triglycerides \>500 mg/dL * History of hypertriglyceridemia-induced pancreatitis * History of gastrointestinal disorder such as dysphagia, swallowing disorder, intestinal motility disorder or prior bowel obstruction * History or presence of any severe medical or psychological condition or chronic conditions/infections that in the opinion of the Investigator would compromise the subject's safety or successful participation in the study * Unable to follow the study protocol * Unable to speak, read and write in English * Pregnant, planning to become pregnant, breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Norm AUC Average by Group (Normalized) | 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2. | Double Blinded CGM used for 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2. |
| Sleep Norm AUC Average by Group (Normalized) | 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2. | Overnight glucose captured by CGM. |
| Wake Norm AUC Average by Group (Normalized) | 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2. | Wake glucose captured by continuous glucose monitoring (CGM). |
| Hypoglycemia Percentage of Time <70 mg/dL Average by Group | 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2. | Ambulatory glucose profile (AGP) reports were examined for the changes in the incidence of hypoglycemia (CGM\<70 mg/dL) |
Countries
United States
Participant flow
Recruitment details
Recruitment Jan 2010 to Mar 2011. Medical Clinic Setting.
Participants by arm
| Arm | Count |
|---|---|
| Welchol Then Placebo 3.75 grams of colesevelam HCl taken at evening meal for 12 weeks, then crossover to placebo taken at evening meal for 12 weeks. | 11 |
| Placebo Then Welchol Placebo taken at evening meal for 12 weeks, then crossover to 3.75 grams of colesevelam HCl taken at evening meal for 12 weeks. | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | Total | Welchol Then Placebo | Placebo Then Welchol |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 9 Participants | 9 Participants |
| Age, Continuous | 59.5 years STANDARD_DEVIATION 8.2 | 59.5 years STANDARD_DEVIATION 9.4 | 59.5 years STANDARD_DEVIATION 7.2 |
| Hypoglycemia percentage of time <70 mg/dL average by group | 0.4 percentage of time <70 mg/dL STANDARD_DEVIATION 0.5 | 0.4 percentage of time <70 mg/dL STANDARD_DEVIATION 0.4 | 0.3 percentage of time <70 mg/dL STANDARD_DEVIATION 0.6 |
| Region of Enrollment United States | 21 participants | 11 participants | 10 participants |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 4 Participants |
| Sleep norm Area under the curve average by group | 159.1 mg/(dL/hr) (normalized) STANDARD_DEVIATION 18.8 | 157.1 mg/(dL/hr) (normalized) STANDARD_DEVIATION 14.3 | 161.2 mg/(dL/hr) (normalized) STANDARD_DEVIATION 23.4 |
| Total norm AUC average | 164.8 mg/(dL/hr) (normalized) STANDARD_DEVIATION 20.9 | 162.2 mg/(dL/hr) (normalized) STANDARD_DEVIATION 16 | 167.7 mg/(dL/hr) (normalized) STANDARD_DEVIATION 25.9 |
| Wake norm area under the curve average by group | 167.5 mg/(dL/hr) (normalized) STANDARD_DEVIATION 22.8 | 165.2 mg/(dL/hr) (normalized) STANDARD_DEVIATION 17.8 | 170.0 mg/(dL/hr) (normalized) STANDARD_DEVIATION 28.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Hypoglycemia Percentage of Time <70 mg/dL Average by Group
Ambulatory glucose profile (AGP) reports were examined for the changes in the incidence of hypoglycemia (CGM\<70 mg/dL)
Time frame: 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Welchol Then Placebo | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | Start of Treatment 1 | 1.2 percentage of time <70 mg/dL | Standard Deviation 1.3 |
| Welchol Then Placebo | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | End of Treatment 1 | 0.8 percentage of time <70 mg/dL | Standard Deviation 1.1 |
| Welchol Then Placebo | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | Start of Treatment 2 | 0.8 percentage of time <70 mg/dL | Standard Deviation 1.2 |
| Welchol Then Placebo | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | End of Treatment 2 | 0.6 percentage of time <70 mg/dL | Standard Deviation 1.2 |
| Placebo Then Welchol | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | End of Treatment 2 | 0.6 percentage of time <70 mg/dL | Standard Deviation 1.1 |
| Placebo Then Welchol | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | Start of Treatment 1 | 0.3 percentage of time <70 mg/dL | Standard Deviation 0.6 |
| Placebo Then Welchol | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | Start of Treatment 2 | 0.7 percentage of time <70 mg/dL | Standard Deviation 1 |
| Placebo Then Welchol | Hypoglycemia Percentage of Time <70 mg/dL Average by Group | End of Treatment 1 | 0.4 percentage of time <70 mg/dL | Standard Deviation 0.6 |
Primary
Sleep Norm AUC Average by Group (Normalized)
Overnight glucose captured by CGM.
Time frame: 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Welchol Then Placebo | Sleep Norm AUC Average by Group (Normalized) | Start of Treatment 1 | 147.4 mg/(dL/hr) normalized | Standard Deviation 16.6 |
| Welchol Then Placebo | Sleep Norm AUC Average by Group (Normalized) | End of Treatment 1 | 148.0 mg/(dL/hr) normalized | Standard Deviation 24 |
| Welchol Then Placebo | Sleep Norm AUC Average by Group (Normalized) | Start of Treatment 2 | 158.8 mg/(dL/hr) normalized | Standard Deviation 31.8 |
| Welchol Then Placebo | Sleep Norm AUC Average by Group (Normalized) | End of Treatment 2 | 172.0 mg/(dL/hr) normalized | Standard Deviation 32.5 |
| Placebo Then Welchol | Sleep Norm AUC Average by Group (Normalized) | End of Treatment 2 | 143.6 mg/(dL/hr) normalized | Standard Deviation 18.6 |
| Placebo Then Welchol | Sleep Norm AUC Average by Group (Normalized) | Start of Treatment 1 | 161.9 mg/(dL/hr) normalized | Standard Deviation 25.7 |
| Placebo Then Welchol | Sleep Norm AUC Average by Group (Normalized) | Start of Treatment 2 | 147.9 mg/(dL/hr) normalized | Standard Deviation 24.4 |
| Placebo Then Welchol | Sleep Norm AUC Average by Group (Normalized) | End of Treatment 1 | 160.2 mg/(dL/hr) normalized | Standard Deviation 27.9 |
Primary
Total Norm AUC Average by Group (Normalized)
Double Blinded CGM used for 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
Time frame: 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Welchol Then Placebo | Total Norm AUC Average by Group (Normalized) | Start of Treatment 1 | 150.8 mg/(dL/hr) normalized | Standard Deviation 10.8 |
| Welchol Then Placebo | Total Norm AUC Average by Group (Normalized) | End of Treatment 1 | 149.9 mg/(dL/hr) normalized | Standard Deviation 17.2 |
| Welchol Then Placebo | Total Norm AUC Average by Group (Normalized) | End of Treatment 2 | 177.9 mg/(dL/hr) normalized | Standard Deviation 33.2 |
| Welchol Then Placebo | Total Norm AUC Average by Group (Normalized) | Start of Treatment 2 | 163.2 mg/(dL/hr) normalized | Standard Deviation 23.5 |
| Placebo Then Welchol | Total Norm AUC Average by Group (Normalized) | End of Treatment 2 | 159.4 mg/(dL/hr) normalized | Standard Deviation 25.3 |
| Placebo Then Welchol | Total Norm AUC Average by Group (Normalized) | End of Treatment 1 | 175.1 mg/(dL/hr) normalized | Standard Deviation 27.4 |
| Placebo Then Welchol | Total Norm AUC Average by Group (Normalized) | Start of Treatment 2 | 159.4 mg/(dL/hr) normalized | Standard Deviation 23.9 |
| Placebo Then Welchol | Total Norm AUC Average by Group (Normalized) | Start of Treatment 1 | 175.9 mg/(dL/hr) normalized | Standard Deviation 29.2 |
Primary
Wake Norm AUC Average by Group (Normalized)
Wake glucose captured by continuous glucose monitoring (CGM).
Time frame: 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Welchol Then Placebo | Wake Norm AUC Average by Group (Normalized) | Start of Treatment 1 | 153.3 mg/(dL/hr) (normalized) | Standard Deviation 11.7 |
| Welchol Then Placebo | Wake Norm AUC Average by Group (Normalized) | End of Treatment 1 | 151.2 mg/(dL/hr) (normalized) | Standard Deviation 16 |
| Welchol Then Placebo | Wake Norm AUC Average by Group (Normalized) | Start of Treatment 2 | 165.2 mg/(dL/hr) (normalized) | Standard Deviation 21.2 |
| Welchol Then Placebo | Wake Norm AUC Average by Group (Normalized) | End of Treatment 2 | 180.9 mg/(dL/hr) (normalized) | Standard Deviation 34.2 |
| Placebo Then Welchol | Wake Norm AUC Average by Group (Normalized) | End of Treatment 2 | 165.2 mg/(dL/hr) (normalized) | Standard Deviation 30.5 |
| Placebo Then Welchol | Wake Norm AUC Average by Group (Normalized) | Start of Treatment 1 | 180.9 mg/(dL/hr) (normalized) | Standard Deviation 32.2 |
| Placebo Then Welchol | Wake Norm AUC Average by Group (Normalized) | Start of Treatment 2 | 163.8 mg/(dL/hr) (normalized) | Standard Deviation 25.6 |
| Placebo Then Welchol | Wake Norm AUC Average by Group (Normalized) | End of Treatment 1 | 180.6 mg/(dL/hr) (normalized) | Standard Deviation 29.6 |