Efficacy of Amlodipine-folic Acid Tablets on Reduction of Blood Pressure and Plasma Homocysteine

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Shenzhen Ausa Pharmed Co.,Ltd
Sponsor:
Collaborators:
Peking University First Hospital
Chinese PLA General Hospital
Capital Medical University
Fudan University
Ruijin Hospital
Nanchang University
First Affiliated Hospital of Fujian Medical University
First Affiliated Hospital of Harbin Medical University
China Medical University, China
Xi’an Jiaotong University College of Medicine
Xuzhou Medical College
Anhui Medical University
Huazhong University of Science and Technology
West China Hospital
Guangdong General Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Information provided by (Responsible Party):
Shenzhen Ausa Pharmed Co.,Ltd
ClinicalTrials.gov Identifier:
NCT01848873
First received: May 4, 2013
Last updated: May 7, 2013
Last verified: May 2013

May 4, 2013
May 7, 2013
January 2013
August 2013   (final data collection date for primary outcome measure)
Combined effective rate of blood pressure and plasma homocysteine reduction [ Time Frame: Blood pressure was examined at baseline and every 2 weeks for a total period of 8 weeks. Blood homocysteine concentrations were measured at baseline and at 4 and 8 weeks of the trial. ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01848873 on ClinicalTrials.gov Archive Site
Blood pressure reduction or plasma homocysteine reduction [ Time Frame: Blood pressure was examined at baseline and every two weeks for a total period of 8 weeks. Blood homocysteine concentrations was examined at baseline and at 4 and 8 weeks of the trial. ] [ Designated as safety issue: No ]
Same as current
24-hour ambulatory blood pressure [ Time Frame: 24-hour ambulatory blood pressure were examined at baseline and at 8 weeks of the trial in 96 participants. ] [ Designated as safety issue: No ]
Same as current
 
Efficacy of Amlodipine-folic Acid Tablets on Reduction of Blood Pressure and Plasma Homocysteine
Efficacy of Amlodipine-folic Acid Tablets on Reduction of Blood Pressure and Plasma Homocysteine in Patients With Mild to Moderate Hypertension and Hyperhomocysteinemia :a Double-blind Randomized Controlled Trial

To evaluate the efficacy of Amlodipine-folic Acid Tablets on reduction of blood pressure and plasma homocystein.

Traditional risk factors are estimated to account for only part of cardiovascular disease (CVD) risk. Non-traditional risk factors such as increased homocysteine concentration are believed to be causally related to CVD. The interactive effect between hypertension and hyperhomocysteinemia on the risk of CVD has received great attention. Methylenetetrahydrofolate reductase (MTHFR) was the main regulatory enzymes for homocysteine metabolism. MTHFR converts 5, 10-methylene-THF into 5-methyl-THF. Polymorphism of MTHFR C677T leads to a reduction in enzyme activity, which may lead to an increased concentration of plasma homocysteine and lower levels of serum folate, particularly in those with low folate intake. In the present study, we sought to assess: (1) the efficacy and safety of Amlodipine-folic Acid Tablets in lowering blood pressure and homocystein in patients with mild to moderate hypertension and hyperhomocysteinemia (hcy≥10μmol/L);(2) if the blood pressure and homocysteine-lowering efficacy of Amlodipine-folic Acid Tablets can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms.

In all, about 756 patients with mild or moderate hypertension and hyperhomocysteinemia will be recruited from about 18 hospitals in different Chinese regions. All hospitals are certified as clinical pharmacology centers by the State Food and Drug Administration (SFDA) in China. Eligible subjects are randomly and double-blindly assigned to one of the three treatment groups: 1) amlodipine tablet (5 mg, control group); 2) amlodipine-folic acid tablet (5mg amlodipine combined with 0.4 mg of folic acid, low FA group); or 3) amlodipine-folic acid tablet (5 mg amlodipine combined with 0.8 mg of folic acid, high FA group), once daily for 8 weeks.

The allocation of participants was programmed by an independent statistical coordinating center, encrypted, and sent to each study center. Tablet containers were labeled only with the name of the trial and the allocated concealment number. The participants, care partners, and all staff directly involved in the trial were blinded to interventions during the period of the trial.

Demographic and clinical information were obtained at baseline. Blood pressure was examined at baseline and every two weeks for a total period of 8 weeks. Blood homocysteine and folate concentrations were examined at baseline and at 4 and 8 weeks of the trial. MTHFR C677T genotypes were determined for each study subject.

All analyses will be performed according to the principle of intention to treat.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Essential Hypertension
  • Drug: Amlodipine
    amlodipine 5mg daily
    Other Name: control
  • Drug: amlodipine-FA tablet, low dose group
    5mg amlodipine combined with 0.4 mg of folic acid, daily.
    Other Name: low dose
  • Drug: amlodipine-FA tablet ,high dose group
    amlodipine 5mg and folic acid 0.8mg daily
    Other Name: high dose
  • Experimental: amlodipine-FA tablet, low dose group
    5mg amlodipine combined with 0.4 mg of folic acid (FA),once daily for 8 weeks.
    Intervention: Drug: amlodipine-FA tablet, low dose group
  • Experimental: amlodipine-FA tablet ,high dose group
    5mg amlodipine combined with 0.8 mg of folic acid (FA), once daily for 8 weeks.
    Intervention: Drug: amlodipine-FA tablet ,high dose group
  • Active Comparator: amolodipine
    5 mg amlodipine, once daily for 8 weeks.
    Intervention: Drug: Amlodipine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
756
August 2013
August 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Aged 18-75 years;
  2. Seated systolic blood pressure (SBP) between 140 mmHg and 180 mmHg and/or seated diastolic blood pressure between 90 mmHg and 110 mmHg;
  3. Plasma homocysteine ≥10umol/L;
  4. Signed the written informed consent.

Exclusion Criteria:

  1. Pregnant women or women within lactation period;
  2. Hypersensitive to calcium channel blocker (CCB) or folic acid;
  3. Easily hypersensitiveness
  4. Diagnosed secondum hypertension or skeptical secondum hypertension;
  5. Severe hypertension (sedentary systolic blood pressure≥180mmHg and/or sedentary diastolic blood pressure≥110mmHg)
  6. Severe diseases:

    1. Cardiovascular system:
    2. Diagnosed cardia insufficiency (NYHAⅢ level and higher); Hypertrophic obstructive cardiomyopathy (HOCM);Clinical significantly valvular disease of the heart (VDH);Acute coronary syndrome or coronary artery interventional therapy or coronary artery bypass graft within three months; Severe arrhythmia such as atrial flutter, atrial fibrillation, atrioventricular block above Ⅱ level, et al;
    3. Alimentary system:
    4. Active virus hepatitis; Any of alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DB) was above 2 times of it's normal value upper limit, albumin (ALB) ≤30g/L;Stomach bulk resect and gastrojejunostomy, stomach intestine malabsorption;
    5. Urinary system:
    6. Serum creatinine≥200μmol/L ; Diagnosed stenosis of renal artery, solitary kidney, renal transplantation;
    7. Endocrine system:
    8. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (fasting glucose≥11.1mmol/L); Diagnosed and uncontrolled hyperthyrosis;
    9. Respiratory system:
    10. Pulmonary heart disease , chronic obstructive lung disease;
    11. Nervous or psyche system:
    12. Transient ischemia attach (TIA) or stoke within 3 months; Severe peripheral nerve or vegetative nerve functional disturbance; Psyche or nervous system dysfunction;Drugs or alcohol dependence.
    13. Others:
    14. Malignant tumor, malnutrition, haematogenesis dysfunction, et al;
  7. Obvious signs or abnormal laboratory examination;
  8. Taking other antihypertensive drugs and unwilling to stop;
  9. Taking folic acid or other Vitamin B groups unwilling to stop.
Both
18 Years to 75 Years
No
Contact: Yong Huo, MD 86-10-66551122-2704 huoyong18@126.com
Contact: Yan Zhang, MD 86-10-66530556 drzhy1108@163.com
China
 
NCT01848873
AUSA-amlodipine
Yes
Shenzhen Ausa Pharmed Co.,Ltd
Shenzhen Ausa Pharmed Co.,Ltd
  • Peking University First Hospital
  • Chinese PLA General Hospital
  • Capital Medical University
  • Fudan University
  • Ruijin Hospital
  • Nanchang University
  • First Affiliated Hospital of Fujian Medical University
  • First Affiliated Hospital of Harbin Medical University
  • China Medical University, China
  • Xi’an Jiaotong University College of Medicine
  • Xuzhou Medical College
  • Anhui Medical University
  • Huazhong University of Science and Technology
  • West China Hospital
  • Guangdong General Hospital
  • Second Affiliated Hospital, School of Medicine, Zhejiang University
Principal Investigator: Yong Huo, MD Peking University First Hospital, Beijing, China
Shenzhen Ausa Pharmed Co.,Ltd
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP