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

• Sponsor: Shenzhen Ausa Pharmed Co.,Ltd (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT01848873
• Collaborator: Peking University First Hospital (Other), Chinese PLA General Hospital (Other), Capital Medical University (Other), Fudan University (Other), Ruijin Hospital (Other), Nanchang University (Other), First Affiliated Hospital of Fujian Medical University (Other), First Affiliated Hospital of Harbin Medical University (Other), China Medical University, China (Other), Health Science Center of Xi'an Jiaotong University (Other), Xuzhou Medical University (Other), Anhui Medical University (Other), Huazhong University of Science and Technology (Other), West China Hospital (Other), Guangdong Provincial People's Hospital (Other), Second Affiliated Hospital, School of Medicine, Zhejiang University (Other)
• Enrollment: 756
• Locations: 16
• Arms: 3
• Duration (Months): 7
• Patients Per Site: 47.3
• Patients Per Site Per Month: 6.8

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: Amlodipine; Drug: amlodipine-FA tablet, low dose group; Drug: amlodipine-FA tablet ,high dose group	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 756 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Jan 1, 2013
• Anticipated Primary Completion Date: Aug 1, 2013
• Anticipated Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: amlodipine-FA tablet, low dose group 5mg amlodipine combined with 0.4 mg of folic acid (FA),once daily for 8 weeks.	Drug: amlodipine-FA tablet, low dose group; 5mg amlodipine combined with 0.4 mg of folic acid, daily.; Other Names: low dose
Experimental: amlodipine-FA tablet ,high dose group 5mg amlodipine combined with 0.8 mg of folic acid (FA), once daily for 8 weeks.	Drug: amlodipine-FA tablet ,high dose group; amlodipine 5mg and folic acid 0.8mg daily; Other Names: high dose
Active Comparator: amolodipine 5 mg amlodipine, once daily for 8 weeks.	Drug: Amlodipine; amlodipine 5mg daily; Other Names: control

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.]

Other Outcome Measures

1. 24-hour ambulatory blood pressure [24-hour ambulatory blood pressure were examined at baseline and at 8 weeks of the trial in 96 participants.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

7. Cardiovascular system:

8. 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;

9. Alimentary system:

10. 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;

11. Urinary system:

12. Serum creatinine≥200μmol/L ; Diagnosed stenosis of renal artery, solitary kidney, renal transplantation;

13. Endocrine system:

14. Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (fasting glucose≥11.1mmol/L); Diagnosed and uncontrolled hyperthyrosis;

15. Respiratory system:

16. Pulmonary heart disease , chronic obstructive lung disease;

17. Nervous or psyche system:

18. 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.

19. Others:

20. Malignant tumor, malnutrition, haematogenesis dysfunction, et al;

21. Obvious signs or abnormal laboratory examination;

22. Taking other antihypertensive drugs and unwilling to stop;

23. Taking folic acid or other Vitamin B groups unwilling to stop.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China	230022
2	Anzhen Hospital,Capital Medical University	Beijing	Beijing	China	100029
3	Peking University First Hospital	Beijing	Beijing	China	100036
4	Chinese PLA General Hospital	Beijing	Beijing	China	100853
5	First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian	China	350005
6	Guangdong General Hospital	Guangzhou	Guangdong	China	510030
7	First Affiliated Hospital of Harbin Medical University	Haibin	Heilongjiang	China	150001
8	Union Hospital, Tongji Medical College,Huazhong University of Science and Technology	Wuhan	Hubei	China	430022
9	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu	China	221006
10	The Second Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi	China	330006
11	First Affiliated Hospital of China Medical University	Shenyang	Liaoning	China	110002
12	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200025
13	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200032
14	First Affiliated Hospital of the School of Medicine, Xi'an Jiaotong University	Xi'an	Shanxi	China	710061
15	West China School of Medicine, West China Hospital ,Sichuan University	Chengdu	Sichuan	China	610041
16	Second Affiliated Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang	China	310009

Sponsors and Collaborators

• 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
• Health Science Center of Xi'an Jiaotong University
• Xuzhou Medical University
• Anhui Medical University
• Huazhong University of Science and Technology
• West China Hospital
• Guangdong Provincial People's Hospital
• Second Affiliated Hospital, School of Medicine, Zhejiang University

Investigators

• Principal Investigator: Yong Huo, MD, Peking University First Hospital, Beijing, CHINA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shenzhen Ausa Pharmed Co.,Ltd
• ClinicalTrials.gov Identifier: NCT01848873
• Other Study ID Numbers: AUSA-amlodipine
• First Posted: May 8, 2013
• Last Update Posted: May 8, 2013
• Last Verified: May 1, 2013

• Keywords provided by Shenzhen Ausa Pharmed Co.,Ltd: Hyperhomocysteinemia; Amlodipine-folic acid tablets; Hypertension; MTHFR C677T
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Hyperhomocysteinemia; Amlodipine

Study Results

No Results Posted as of May 8, 2013