A Randomized, Double-Blind, Controlled Trial on the Homocysteine-Lowering Effects of Different Doses of Folic Acid Among Patients With Hypertension According to Methylenetetrahydrofolate Reductase C677T Genotypes
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 3,600
- Locations
- 5
- Primary Endpoint
- Percentage decrease in blood homocysteine levels by the end of the 8th week from baseline.
Study Overview
Brief Summary
This is a multicenter, randomized, double-blind, controlled clinical trial. It aims to investigate the effects of different doses of folic acid on lowering homocysteine (Hcy) in patients with hypertension with different genotypes of MTHFR C677T and to determine a dose-response relationship.
This study consists of 3 phases: screening ( 2-10 days ), run-in period (0-2 weeks), and double-blind treatment (8 weeks). Follow-up visits will take place at the beginning of both the run-in period and the double-blind treatment period, and at the end of the 2nd, 4th, 6th, and 8th weeks. Hypertensive patients demonstrating good tolerance and adherence to angiotensin converting enzyme inhibitor (ACEI) drugs and who have already been genotyped for MTHFR C677T polymorphism may pass over the run-in period and directly enter the double-blind randomized treatment period. No medications that could affect the assessment of efficacy may be taken during any stage of the study.
Detailed Description
Phase I: Screening（V0）
Phase I takes place for about 2-10 days. The purpose is to obtain informed consent and make a preliminary assessment of the patient.
At the first screening visit (V0), or prior to the official treatment visit, a clinical examination will be performed to determine the patient's clinical diagnosis and to determine eligibility for inclusion in the study. General demographic information and questions related to the inclusion/exclusion criteria of this study will be obtained. Additionally, this will be the time to discuss the impact of participant vacation/travel plans on adherence and compliance with the trial protocol.
Before carrying out any research procedures, the purpose of the study and study procedures will be explained and the participant's informed consent will be obtained.
Clinical Diagnosis and Assessment: Prior to the start of the Run-in Period, baseline data and efficacy evaluation data will be collected according to the study flow chart; blood and urine samples will also be collected.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 45 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Participants meeting any of the following criteria may not participate in this study:
- •（1）Women who are pregnant and/or lactating; or women who intend to conceive within a year;
- •（2）History of allergies to enalapril, folic acid or other components of the compound drug;
- •（3）History of adverse reactions or intolerance to enalapril or other ACE inhibitors, or drugs or supplements containing folic acid;
- •（4）Diagnosis or suspicion of secondary hypertension;
- •（5）Known serious medical conditions, including: Cardiovascular: patients with clinically diagnosed cardiac dysfunction (NYHA class III and above), hypertrophic obstructive cardiomyopathy, clinically significant valvular heart disease, acute coronary syndrome within the last 3 months, or percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG); or abnormal pre-enrollment ECG test results with clinically significant arrhythmias (atrial flutter, atrial fibrillation, grade II-III atrioventricular block, etc.); Digestive: a previous diagnosis of various types of viral hepatitis that are still in the active phase; abnormal pre-enrollment liver function test results (ALT, AST, GGT, TBIL, or DBIL 3 times higher than normal, ALB ≤ 30g/L); gastrectomy and/or gastrojejunostomy; gastrointestinal dysfunction; Urinary: pre-enrollment serum creatinine greater than 200μmol/L; clinical diagnosis of renal artery stenosis, isolated kidney, kidney transplantation and/or other diseases; Endocrine: type 1 diabetes or uncontrolled type 2 diabetes (fasting blood glucose above 11.1 mmol/L at pre-enrollment); previous diagnosis of hyperthyroidism and failure to correct; Respiratory: pulmonary heart disease; chronic obstructive pulmonary disease; Neuropsychiatric: recent transient ischemic attack or stroke (within the last 3 months); peripheral or severe autonomic dysfunction; mental or nervous system dysfunction, inability to express desire; known drug or alcohol dependence; Malignancy, malnutrition, hematopoietic disorders and other serious diseases.
- •（6）Significant signs of abnormalities as seen in laboratory tests or physical characteristics, which, at the discretion of the investigators, indicates that the patient is experiencing a serious illness or, may affect the observation and evaluation of the drug's efficacy or adverse events, or renders the patient unsuitable for participating in this study;
- •（7）Patients currently taking folate, B12, or B6, or any compounds containing them, who express an inability or a refusal to stop usage;
- •（8）Regular usage of folic acid supplements or compounds containing folic acid in the past 3 months;
- •（9）Participation in a clinical trial for a drug that has not yet been officially approved for marketing within one month prior to the first visit.
Arms & Interventions
0 mg folic acid
Enalapril Maleate (10mg) with 0 mg folic acid
Intervention: Folic Acid (Drug)
0 mg folic acid
Enalapril Maleate (10mg) with 0 mg folic acid
Intervention: Enalapril (Drug)
0.4mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.4mg)
Intervention: Folic Acid (Drug)
0.4mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.4mg)
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
0.6mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.4mg) with 0.2 mg folic acid
Intervention: Folic Acid (Drug)
0.6mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.4mg) with 0.2 mg folic acid
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
0.8mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg)
Intervention: Folic Acid (Drug)
0.8mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg)
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
1.2mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 0.4 mg folic acid
Intervention: Folic Acid (Drug)
1.2mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 0.4 mg folic acid
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
1.6mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 0.8 mg folic acid
Intervention: Folic Acid (Drug)
1.6mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 0.8 mg folic acid
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
2.0mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 1.2 mg folic acid
Intervention: Folic Acid (Drug)
2.0mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 1.2 mg folic acid
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
2.4mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 1.6 mg folic acid
Intervention: Folic Acid (Drug)
2.4mg Folic acid
Enalapril Maleate and Folic Acid Tablets (Yiye) (10mg:0.8mg) with 1.6 mg folic acid
Intervention: Enalapril Maleate and Folic Acid Tablets (Yiye) (Drug)
Outcomes
Primary Outcomes
Percentage decrease in blood homocysteine levels by the end of the 8th week from baseline.
Time Frame: by the end of the 8th week from the baseline
Hcy percent decrease =（baseline Hcy - end Hcy) /baseline Hcy \*100%
Secondary Outcomes
- Percentage of increase in blood folate levels by the end of the 8th week from baseline.(by the end of the 8th week from the baseline)
- Magnitude of decrease in blood homocysteine by the end of the 8th week from baseline.(by the end of the 8th week from the baseline)
- Magnitude of increase in blood folate levels by the end of the 8th week from baseline.(by the end of the 8th week from the baseline)