Clinical trial NCT05807711: Efficacy of L-methylfolate and Methylcobalamine in Treating Resistant Hypertension Associated with Elevated Serum Homocysteine in Hemodialysis Patients.
Official title: Efficacy of L-methylfolate and Methylcobalamine in Treating Resistant Hypertension Associated with Elevated Serum Homocysteine in Hemodialysis Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End Stage Renal Disease
Hypertension, Renal
Keywords: L-methylfolate
methylcobalamine
homocysteine
Lead sponsor: Alexandria University
Sponsor class: OTHER
First posted: 2023-04-11
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open-label, single-center, randomized controlled trial
Primary purpose: TREATMENT

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: 1. Ethical committee approval has been obtained from Ethics committee of Faculty of Medicine, Alexandria University
2. Agreement from all participants should be taken in this clinical study by assigning an informed consent
3. 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
4. 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.
5. A blood sample will be collected for homocysteine measurement at baseline
6. 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.
7. 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
8. As a measurement of the prognosis of elevated homocysteine, we should follow the development of myocardial infarction, stroke and cardiovascular events for 3 months
9. The appropriate statistical tests will be held according to the study design and parameters to evaluate the significance of the results
10. Results, conclusion, discussion and recommendations will be given

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

Primary outcomes:
measure: average pre-dialysis blood pressure target of ≤ 140/90 mm Hg or an average post-dialysis blood pressure target of ≤ 130/80 mm Hg
timeFrame: 3 months
Secondary outcomes:
measure: myocardial infarction, stroke and cardiovascular events.
timeFrame: 3 months
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Faculty of Pharmacy, Alexandria University
Study officials:
affiliation: Professor of Pharmacology & Toxicology, Alexandria University
name: Hanan M El-gowelli, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor of Internal Medicine, Alexandria University
name: Hesham A Elghoneimy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor of Clinical Pharmacy, Alexandria University
name: Noha A Hamdy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Master's student in Clinical Pharmacy and Pharmacy Practice, Alexandria University.
name: Mohamed S Salem, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cianciolo G, La Manna G, Coli L, Donati G, D'Addio F, Persici E, Comai G, Wratten M, Dormi A, Mantovani V, Grossi G, Stefoni S. 5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients. Am J Nephrol. 2008;28(6):941-8. doi: 10.1159/000142363. Epub 2008 Jun 30.
citation: Friedman AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH. The kidney and homocysteine metabolism. J Am Soc Nephrol. 2001 Oct;12(10):2181-2189. doi: 10.1681/ASN.V12102181.
citation: Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. doi: 10.1056/NEJMoa041031.
citation: Li J, Jiang S, Zhang Y, Tang G, Wang Y, Mao G, Li Z, Xu X, Wang B, Huo Y. H-type hypertension and risk of stroke in chinese adults: A prospective, nested case-control study. J Transl Int Med. 2015 Oct-Dec;3(4):171-178. doi: 10.1515/jtim-2015-0027. Epub 2015 Dec 30.