Efficacy of L-methylfolate and Methylcobalamine in Treating Hypertension and Its Impact on Serum Homocysteine in Hemodialysis Patients With Resistant Hypertension

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to evaluate the efficacy of L-methylfolate in combination with methylcobalamine in reducing homocysteine blood levels in hypertensive end-stage renal disease patients on regular hemodialysis and its association with blood pressure control in treatment of resistant hypertension

Detailed Description
-----------------
Ethical committee approval has been obtained from Ethics committee of Faculty of Medicine, Alexandria University Agreement from all participants should be taken in this clinical study by assigning an informed consent Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension will be recruited from hemodialysis unit in Alexandria University Hospitals Patients will be screened for resistant hypertension as determined by the mean of mid-week pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg over a period of one month. A blood sample will be collected for homocysteine measurement at baseline Patients will be randomized using simple randomization technique via computer based program to take one tablet daily containing L-methylfolate and methylcobalamine or no treatment. Patients will be followed over a period of 3 months after which blood pressure measurement and blood sampling would be repeated and compared to baseline values As a measurement of the prognosis of elevated homocysteine, we should follow the development of myocardial infarction, stroke and cardiovascular events for 3 months The appropriate statistical tests will be held according to the study design and parameters to evaluate the significance of the results Results, conclusion, discussion and recommendations will be given

Official Title
-----------------
Efficacy of L-methylfolate and Methylcobalamine in Treating Hypertension and Its Impact on Serum Homocysteine in Hemodialysis Patients With Resistant Hypertension

Conditions
-----------------
End Stage Renal Disease, Hypertension, Renal

Intervention / Treatment
-----------------
* Drug: L-Methyl Folate and methylcobalamine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension as determined by pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg despite the use of three or more drugs Exclusion Criteria: Age > 75 years Excessive use of alcohol or smoking Severe hepatic impairment Acute kidney injury on top of chronic kidney disease Pregnant females Allergy or intolerance to any component of the formulation Medication side effects (methotrexate, theophylline, phenytoin, and cyclosporine) or any drug proven to cause hyperhomocysteinemia

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: open-label, single-center, randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: Intervention group<br>Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension as determined by pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg despite the use of three or more drugs. Patients will be assigned to take one tablet daily containing L-methylfolate and methylcobalamine. Patients will be followed over a period of 3 months after which blood pressure measurement and blood sampling would be repeated and compared to baseline values. | Drug: L-Methyl Folate and methylcobalamine<br>* Dietary supplement labeled to contain methylfolate 800 micrograms and methylcobalamine 1000 micrograms<br>|
| No Intervention: No Intervention: Control group<br>Adult end stage renal disease patients maintained on hemodialysis three times a week for at least 3 months with resistant hypertension as determined by pre-dialysis BP > 140/90 mm Hg, post-dialysis BP > 130/80 mm Hg despite the use of three or more drugs. Patients will be followed over a period of 3 months after which blood pressure measurement and blood sampling would be repeated and compared to baseline values. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| average pre-dialysis blood pressure target of ≤ 140/90 mm Hg or an average post-dialysis blood pressure target of ≤ 130/80 mm Hg | To achieve an average pre-dialysis blood pressure target of ≤ 140/90 mm Hg or an average post-dialysis blood pressure target of ≤ 130/80 mm Hg. This should be parallel to lowering of serum homocysteine compared to baseline values | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myocardial infarction, stroke and cardiovascular events. | As a measurement of the prognosis patients will be followed up for the development of myocardial infarction, stroke and cardiovascular events for 3 months. | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
L-methylfolate, methylcobalamine, homocysteine