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

Phase 2

• Conditions: Essential Hypertension
• Interventions: Drug: amlodipine-FA tablet, low dose group; Drug: amlodipine-FA tablet ,high dose group; Drug: Amlodipine

• Registration Number: NCT01848873
• Lead Sponsor: Shenzhen Ausa Pharmed Co.,Ltd

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 2013-01
• Status Verified: 2013-05
• Study First Submitted: 2013-05-04
• Study First Submitted QC: 2013-05-07
• Last Update Submitted: 2013-05-07
• Study First Posted: 2013-05-08
• Last Update Posted: 2013-05-08
• Primary Completion: 2013-08
• Study Completion: 2013-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 756

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
amlodipine-FA tablet, low dose group	amlodipine-FA tablet, low dose group	5mg amlodipine combined with 0.4 mg of folic acid (FA),once daily for 8 weeks.
amlodipine-FA tablet ,high dose group	amlodipine-FA tablet ,high dose group	5mg amlodipine combined with 0.8 mg of folic acid (FA), once daily for 8 weeks.
amolodipine	Amlodipine	5 mg amlodipine, once daily for 8 weeks.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (16)

The Affiliated Hospital of Xuzhou Medical College; 🇨🇳 Xuzhou, Jiangsu, China

The First Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

First Affiliated Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

Guangdong General Hospital; 🇨🇳 Guangzhou, Guangdong, China

Union Hospital, Tongji Medical College,Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

The Second Affiliated Hospital Of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

First Affiliated Hospital of the School of Medicine, Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

West China School of Medicine, West China Hospital ,Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China

First Affiliated Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

Second Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Anzhen Hospital,Capital Medical University; 🇨🇳 Beijing, Beijing, China

First Affiliated Hospital of Harbin Medical University; 🇨🇳 Haibin, Heilongjiang, China

Zhongshan Hospital Fudan University; 🇨🇳 Shanghai, Shanghai, China

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China