Assess the Effect of Bisoprolol on Glycemic Level in Type II Diabetic Patients With Suboptimal Blood Pressure Control (GIANT Study)

This study has been completed.
Sponsor:
Collaborator:
Merck Ltd.
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01066039
First received: February 8, 2010
Last updated: September 5, 2013
Last verified: September 2013
  Purpose

This is a 24-week, prospective, multicenter, open-label, single arm study to assess the effect of bisoprolol on glycemic level in Type II diabetes mellitus (DM) controlled subjects with hypertension. The hypothesis of study is that there is no change in glycemic level and lipid metabolism as determined by HbA1C using bisoprolol in Type II DM subjects with suboptimal blood pressure (BP) control.


Condition Intervention Phase
Hypertension
Diabetes Mellitus, Type II
Drug: Bisoprolol
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Glycemic control measured by differences in the change from baseline HbA1C [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean blood pressure calculated by 2 consecutive measurements with 2 minute intervals in sitting position after having seated quietly for at least 10 minutes [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: No ]
  • Insulin sensitivity as determined by HOMA-IR (Homeostasis model assessment-insulin resistance) [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: No ]
  • Lipid metabolism as determined by lipid profile (total cholesterol, LDL, HDL, TC) [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: No ]
  • Safety assessments includes adverse experiences, physical examination, vital signs and laboratory safety studies [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: Yes ]
  • Production ability of insulin in pancreas as determined by c-peptide and insulin [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: Yes ]
  • Microalbuminuria as determined by albumin/creatinine ratio [ Time Frame: From baseline to 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 201
Study Start Date: April 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bisoprolol Drug: Bisoprolol
5 mg bisoprolol will be given once daily (o.d.) in the morning. During the 24-week treatment period, bisoprolol will be titrated upward until a dosage that lowers BP to <130/80 mmHg during the first 8-weeks of treatment (Up-titration). The maximum dosage will be 10 mg once daily. Subjects will be in the maintenance period for next 16-weeks.
Other Name: Concor, Concor Plus, ConcorCor or Lodoz

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 β-blocker might have adverse effects in subjects with diabetes on glucose metabolism, but some data shows that highly β-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 Type II DM patient with suboptimal BP control.

After prescreening period, each enrolled subject with type II DM and suboptimal BP control will underwent 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 <130/80 mmHg during the first 2 month of treatment. The maximum dosage of bisoprolol will be 10 mg o.d. Following 6 month of added bisoprolol therapy, all efficacy and safety measurement will be repeated.

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

OBJECTIVES

Primary objective:

  • To assess the effect of bisoprolol on glycemic control measured by differences in the change from baseline HbA1C in Type II DM subjects with suboptimal BP control

Secondary objectives:

  • To evaluate the effect of bisoprolol as add-on therapy, on blood pressure in Type II DM subjects with suboptimal BP control
  • To evaluate the effect of bisoprolol as add-on therapy, on insulin sensitivity as determined by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR)
  • To evaluate the effect of bisoprolol as add-on therapy, on lipid metabolism as determined by lipid profile in Type II DM subjects with suboptimal BP control
  • To evaluate the safety and tolerability of bisoprolol in Type II DM subjects with suboptimal BP control
  • To assess the effect of bisoprolol combination therapy on insulin and c-peptide in type II diabetic patients with suboptimal blood pressure control compared to baseline
  • To assess the effect of bisoprolol combination therapy on microalbumin and albumin/creatinine ratio in type II diabetic patients with suboptimal blood pressure control compared to baseline.
  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >18 years of age and <80 years of age
  • Subjects with type II diabetes
  • Repeated BP measurement >130/80 mmHg while receiving antihypertensive medication, except β-blockers
  • Stable antidiabetic regimen during the 12 weeks prior to screening
  • Signed written informed consent

Exclusion Criteria:

  • Patients who are treated with insulin
  • Change in two HbA1 levels measured more than 4 weeks apart for the past six months is ≥1% (the last HbA1c is measured within 4 weeks)
  • Secondary hypertension
  • Renal impairment (creatinine > 150 umol/L or 1.7 mg/dl)
  • Cardiovascular disease (uncontrolled or symptomatic arrhythmias, unstable angina, sick sinus syndrome or second or third degree heart block, bradycardia [<50bpm], congestive heart failure, myocardial infarction, stroke within the previous months)
  • Required 3 or more antihypertensive medications for BP control or patients who show SBP ≥ 180 mmHg or DBP ≥110 mmHg at baseline
  • Insulin-dependent diabetes mellitus
  • Uncontrolled DM with HbA1C >9%
  • BMI >40 kg/m2
  • Pulmonary disease (chronic obstructive pulmonary disease [COPD], bronchial asthma)
  • Systemic disease, including cancer
  • Psychological illness/conditions that would interfere with subject's ability to understand or complete the requirement of the study
  • Contraindications for β-blocker
  • Pregnancy or lactating women (*Note: Subject is a non-sterilized premenopausal female and agrees to use 2 barrier methods of contraception to prevent pregnancy during the study and for 14 days after last dose of study medication may participate in the study
  • Use of an investigational drug within 30 days of entry to the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01066039

Locations
Korea, Republic of
Seoul St. Mary´s Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Merck KGaA
Merck Ltd.
Investigators
Study Director: Medical Responsible Merck Ltd. South Korea
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01066039     History of Changes
Other Study ID Numbers: EMR 200006-509
Study First Received: February 8, 2010
Last Updated: September 5, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Merck KGaA:
Bisoprolol
Hypertension
Diabetes mellitus, Type II
Blood pressure
Glycemic level

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Bisoprolol
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014