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

Essential Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01848873
• Other study ID #: AUSA-amlodipine
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: May 4, 2013
• Last updated: May 7, 2013
• Start date: January 2013
• Est. completion date: August 2013

Study information

• Verified date: May 2013
• Source: Shenzhen Ausa Pharmed Co.,Ltd
• Contact: Yong Huo, MD
• Phone: 86-10-66551122-2704
• Email: huoyong18[@]126.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 756
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 (NYHA? 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 ? 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hyperhomocysteinemia
• Hypertension

Intervention

Drug:
• Amlodipine
amlodipine 5mg daily
• amlodipine-FA tablet, low dose group
5mg amlodipine combined with 0.4 mg of folic acid, daily.
• amlodipine-FA tablet ,high dose group
amlodipine 5mg and folic acid 0.8mg daily

Locations

Country	Name	City	State
China	Anzhen Hospital,Capital Medical University	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	West China School of Medicine, West China Hospital ,Sichuan University	Chengdu	Sichuan
China	First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	First Affiliated Hospital of Harbin Medical University	Haibin	Heilongjiang
China	Second Affiliated Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	Union Hospital, Tongji Medical College,Huazhong University of Science and Technology	Wuhan	Hubei
China	First Affiliated Hospital of the School of Medicine, Xi'an Jiaotong University	Xi'an	Shanxi
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu

Sponsors (17)

Lead Sponsor

Collaborator

Shenzhen Ausa Pharmed Co.,Ltd

Anhui Medical University, Capital Medical University, China Medical University, China, Chinese PLA General Hospital, First Affiliated Hospital of Fujian Medical University, First Affiliated Hospital of Harbin Medical University, Fudan University, Guangdong General Hospital, Huazhong University of Science and Technology, Nanchang University, Peking University First Hospital, Ruijin Hospital, Second Affiliated Hospital, School of Medicine, Zhejiang University, West China Hospital, Xi’an Jiaotong University College of Medicine, Xuzhou Medical College

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	24-hour ambulatory blood pressure		24-hour ambulatory blood pressure were examined at baseline and at 8 weeks of the trial in 96 participants.	No
Primary	Combined effective rate of blood pressure and plasma homocysteine reduction		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.	No
Secondary	Blood pressure reduction or plasma homocysteine reduction		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.	No