MATCHED (MC-1 and ACE Therapeutic Combination for Hypertensive Diabetics)

This study has been completed.
Sponsor:
Information provided by:
Medicure
ClinicalTrials.gov Identifier:
NCT00157729
First received: September 8, 2005
Last updated: October 30, 2006
Last verified: October 2006
  Purpose

The purpose of this study is to determine whether MC-1 alone and in combination with an ACE inhibitor is effective in reducing blood pressure and metabolic dysfunctions associated with diabetes


Condition Intervention Phase
Diabetes Mellitus Type 2
Hypertension
Metabolic Syndrome
Drug: pyridoxal-5'-phosphate with and without ACE inhibitor
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Evaluation of the Effects of MC-1 Alone and in Combination With an ACE Inhibitor on Ambulatory Blood Pressure and Metabolic Function in Hypertensive Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Medicure:

Primary Outcome Measures:
  • Effects on blood pressure:
  • Determine the efficacy of MC-1 and of the combination of MC-1/ACE inhibitor on blood pressure as measured by mean daytime ambulatory systolic blood pressure.
  • Effects on metabolic function:
  • Determine the efficacy of MC-1 and of the combination of MC-1/ACE inhibitor on metabolic function as measured by insulinemia, fasting serum glucose, glycated hemoglobin, and triglycerides.

Secondary Outcome Measures:
  • To compare the effects of the different treatment regimens as measured by:
  • mean change from baseline in mean daytime ambulatory diastolic BP
  • mean change from baseline in mean 24 hour and mean night-time ambulatory systolic BP
  • mean changes from baseline in mean 24 hour, mean daytime and mean night-time pulse pressure
  • mean changes from baseline in clinic trough sitting systolic BP (SiSBP)
  • mean changes from baseline in mean 24 hour, and mean night-time ambulatory diastolic BP
  • mean changes from baseline in clinic trough sitting diastolic BP (SiDBP)
  • mean change in endothelial function as measured by mean changes in different markers such as ICAM-1, VCAM-1, E-selectin and albuminuria
  • mean changes in C-reactive protein (CRP)
  • mean changes in homocysteine
  • mean changes in creatinine

Estimated Enrollment: 160
Study Start Date: August 2004
Estimated Study Completion Date: July 2005
Detailed Description:

Hypertension is an extremely common co-morbid condition in diabetics, affecting up to 11 million patients, depending on obesity, ethnicity and age. Hypertension substantially increases the risk of both macrovascular and microvascular complications including stroke, coronary artery disease, peripheral vascular disease, retinopathy, nephropathy and possibly neuropathy.

In recent years, adequate data from well-designed randomized clinical trials have demonstrated the effectiveness of aggressive treatment of hypertension in reducing diabetic complications. In the epidemiological UK Prospective Diabetes Study (UKPDS), each 10 mmHg decrease in mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes, 15% for deaths related to diabetes, 11% for myocardial infarction and 13% for microvascular complications. Currently the consensus guidelines recommend a blood pressure target of <130/80 mmHg in diabetic patients with hypertension, even though they recognize many people will require three or more drugs to reach this goal.

MC-1 is a naturally occurring metabolite of vitamin B6, and thus has very low toxicity. Evidence from pre-clinical studies suggests that MC-1 has beneficial effects on hypertension and metabolic dysfunction. This trial will assess the effects of MC-1 alone and MC-1 in combination with an ACE inhibitor compared to placebo on hypertension and parameters of metabolic function in type 2 diabetic patients.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus treated with diet, oral hypoglycaemic agents or insulin) for a minimum of 2 years (24 months)
  • Systolic hypertension prior to entry into the washout period. At Visit 3 patients must have a mean sitting systolic blood pressure in the range of 140-180 mmHg, and a mean sitting diastolic blood pressure <110mmHg
  • A mean daytime ambulatory systolic blood pressure greater than or equal to 135 mm Hg at baseline

Exclusion Criteria:

  • Poorly controlled type 2 diabetes mellitus (HbA1c ≥ 10%)
  • Secondary hypertension of any aetiology, such as renal artery stenosis, coarctation of the aorta or pheochromocytoma
  • History of malignant hypertension
  • Body mass index > 37
  • Single functioning kidney
  • Known sensitivity or intolerance to angiotensin-converting enzyme inhibitors
  • History of angioedema
  • Known syncopal disorder
  • Pregnant woman or a woman of childbearing potential who is sexually active and not using an appropriate method of birth control (double barrier or oral contraceptives)
  • Concomitant therapy with any antihypertensive medications, including those used for indications other than hypertension (e.g., diuretics for any reason, minoxidil for hair loss, propranolol HCl for migraine, terazosin HCl for benign prostatic hyperplasia, 5-phosphodiesterase inhibitors (Viagra, Cialis, Levitra) within 48 hours of clinic visit, ACE-inhibitors for congestive heart failure, or any agent which could cause a change in blood pressure), except for stable doses of NSAIDs, or tricyclic agents taken at bedtime. Patients who are unwilling to discontinue these medications or patients in whom the Investigator feels it is clinically inappropriate to discontinue these medications should not participate in the study
  • Concomitant therapy with lithium and/or major psychotropic agents such as phenothiazines
  • Concomitant therapy with oral steroids or ACTH
  • Concomitant therapy with cold and/or flu medications containing sympathomimetic agents. Intermittent use of therapies containing ephedrine is permitted except within 72 hours of clinic visits for mean trough SiSBP
  • Concomitant therapy with any vitamin supplement that may contain pyridoxine or pyridoxine derivative such as pyridoxal phosphate or pyridoxal
  • Hypertension induced by oral contraceptives. Replacement hormones (thyroid, testosterone, estrogens) are permitted if the patient has been on a stable dose for at least three months
  • Existing symptomatic cerebro-vascular disease including previous transient ischemic attack (TIA) or stroke within 12 months prior to screening
  • Myocardial infarction, percutaneous coronary intervention and coronary artery bypass surgery within 6 months prior to screening
  • Clinically significant AV conduction disturbance, i.e., second or third degree AV block, sick sinus syndrome or clinically significant bradycardia (resting heart rate < 60 beats/minute) without a permanent pacemaker
  • Presence of atrial flutter or atrial fibrillation
  • Potentially life-threatening ventricular arrhythmias, decompensated valvular disease, presence of hemodynamically significant obstructive valvular disease, or cardiomyopathy
  • Serum potassium < 3.5 or > 5.5 mEq/L
  • The presence of severe hepatic impairment as manifested by AST (SGOT) > 2.5 times the upper limit of normal or ALT (SGPT) > 2.5 times the upper limit of normal
  • Any clinically significant laboratory value which in the Investigator’s judgement could be clinically significant to the outcome of this study. This includes, but is not limited to, hematocrit, haemoglobin or platelet count
  • Any moderate to severe renal impairment, as manifested by serum creatinine more than 200 micromol/L
  • A history of clinically important gastrointestinal resection, malabsorption or cirrhosis of the liver
  • Any concurrent severe disease that, in the Investigator’s judgement, could preclude participation or survival
  • Use of any investigational drug or device, or participation in any drug study during or within 30 days prior to baseline
  • Inability to be taken off of all current antihypertensive medications
  • Unwillingness or inability to give consent or to follow the protocol procedures
  • Arm circumference greater than 41 cm
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00157729

Locations
Canada, Quebec
Centre Hospitalier Université Laval
Sainte-Foy, Quebec, Canada, G1V 4G2
Sponsors and Collaborators
Medicure
Investigators
Principal Investigator: Yves Lacourciere, MD, FRCP Centre Hospitalier de l'Universite Laval
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00157729     History of Changes
Other Study ID Numbers: MC6021-CL-04001
Study First Received: September 8, 2005
Last Updated: October 30, 2006
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Medicure:
Hypertension
antihypertensive agents
diabetes mellitus type 2
metabolic syndrome

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Metabolic Syndrome X
Syndrome
Cardiovascular Diseases
Disease
Endocrine System Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Insulin Resistance
Metabolic Diseases
Pathologic Processes
Vascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Pyridoxal Phosphate
Enzyme Inhibitors
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on October 22, 2014