Clinical trial NCT01066039: Phase 4 Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II Diabetic Subjects With Suboptimal Blood Pressure Control
Official title: A Prospective, Multi-center, Open-label, Single Arm Study to Assess the Effect of Bisoprolol on Glycemic Level in Type II DIAbetic patieNTs With Suboptimal Blood Pressure Control (GIANT Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Diabetes Mellitus, Type II
Keywords: Bisoprolol
Hypertension
Diabetes mellitus, Type II
Blood pressure
Glycemic level
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Ltd.
First posted: 2010-02-10
Enrollment: 202
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a 24-week, prospective, multicenter, open-label, single-arm study to assess the effect of bisoprolol on glycemic level in Type 2 diabetes mellitus (T2DM) controlled subjects with hypertension. The hypothesis of study is that there is no change in glycemic level and lipid metabolism as determined by glycosylated hemoglobin (HbA1c) using bisoprolol in T2DM subjects with suboptimal blood pressure (BP) control.

Detailed description: Diabetes mellitus and hypertension are two of the most common chronic conditions, and each predisposes to accelerated atherosclerosis, cardiovascular disease, and death. There has been a concern that beta-blocker might have adverse effects in subjects with diabetes on glucose metabolism, but some data shows that highly beta-1 selective agents such as bisoprolol are essentially free of metabolic disturbances involving blood sugar, insulin sensitivity and lipids.

This is a prospective, multicenter, single-arm, open-label study to assess the glycemic effect of bisoprolol in T2DM subjects with suboptimal BP control.

After pre-screening period, each enrolled subject with T2DM and suboptimal BP control will undergo laboratory test for efficacy and safety measurement. After that, subject will continue his/her usual dosage of antihypertensive medication and bisoprolol will be added.

Subjects will be instructed to continue their diet and level of physical activity and to attempt to maintain current body weight until completion of the study.

Bisoprolol will be titrated upward until a dosage that lowers BP to less than 130/80 millimeter of mercury (mmHg) during the first 2 months of treatment. The maximum dosage of bisoprolol will be 10 mg once daily. Following 6 month of added bisoprolol therapy, all efficacy and safety measurements will be repeated.

The duration of study will be up to 24 weeks for each subject.

Objectives

Primary objective:

* To assess the effect of bisoprolol on glycemic control measured by change from baseline in HbA1c in T2DM subjects with suboptimal BP control

Secondary objectives:

* To evaluate the effects of bisoprolol, as add-on therapy, on BP in T2DM subjects with suboptimal BP control
* To evaluate the effects of bisoprolol, as add-on therapy, on insulin sensitivity as determined by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
* To evaluate the effects of bisoprolol, as add-on therapy, on lipid metabolism as determined by lipid profile in T2DM subjects with suboptimal BP control
* To evaluate the safety and tolerability of bisoprolol in T2DM subjects with suboptimal BP control
* To assess the effects of bisoprolol combination therapy on insulin and c-peptide in T2DM subjects with suboptimal BP control compared to baseline
* To assess the effects of bisoprolol combination therapy on microalbumin and albumin/creatinine ratio in T2DM subjects with suboptimal BP control compared to baseline

Eligibility criteria: Inclusion Criteria:

* Age of 20 years or older and less than 80 years
* Subjects with T2DM
* Subjects who have failed to achieve an appropriate BP level as a result of treatment with any antihypertensive drug other than beta blockers - that is, with BP inadequately controlled to greater than or equal to (\>=) 130/80 mmHg. However, those who have used a beta blocker before 12 weeks can be enrolled
* Subjects who underwent stable anti-diabetic regimen during the 12 weeks prior to screening
* Signed written informed consent

Exclusion Criteria:

* Ongoing insulin therapy
* Change in two HbA1c levels measured at an interval of 4 weeks or longer for the previous 6 months is at least 1% (the last HbA1c is measured within 4 weeks)
* Secondary hypertension
* Subjects with renal impairment (creatinine greater than 150 micromol per liter or 1.7 milligram per deciliter)
* Cardiovascular disease (uncontrolled or symptomatic arrhythmia, unstable angina, sick sinus syndrome, second or third degree atrioventricular (AV) block, bradycardia \[less than 50 beats per minute\], congestive heart failure, myocardial infarction, cerebral infraction attached within 12 weeks)
* Subjects requiring BP control by at least 3 different antihypertensive drugs, or with either systolic blood pressure (SBP) \>=180 mmHg or diastolic blood pressure (DBP) \>=110 mmHg at baseline
* Subjects with type 1 diabetes mellitus (T1DM)
* Uncontrolled diabetes with HbA1c \>9%
* BMI \>40 kilogram per square meter (kg/m\^2)
* Pulmonary disease (chronic obstructive pulmonary disease \[COPD\], bronchial asthma)
* Other patients considered by the investigator to be not eligible for participation in this study for a legal or mental reason
* Contraindications for beta-blocker
* Pregnant or lactating women
* Use of an investigational drug within 30 days of entry to the study

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 6
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Month 3
timeFrame: Baseline, Month 3
measure: Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Blood Pressure (BP) at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Months 3 and 6
timeFrame: Baseline, Months 3 and 6
measure: Change From Baseline in Insulin Level at Months 3 and 6
timeFrame: Baseline, Months 3 and 6
measure: Change From Baseline in C-Peptide Level at Months 3 and 6
timeFrame: Baseline, Months 3 and 6
measure: Change From Baseline in Total Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol and Triglyceride Level at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Albumin/Creatinine Ratio at Month 6
timeFrame: Baseline, Month 6
measure: Change From Baseline in Microalbumin Level at Month 6
timeFrame: Baseline, Month 6
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Month 6
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary´s Hospital
Study officials:
affiliation: Merck Ltd.
name: Medical Responsible
role: STUDY_DIRECTOR
References: