Efficacy of L-methylfolate and Methylcobalamine in Treating Resistant Hypertension Associated with Elevated Serum Homocysteine in Hemodialysis Patients.

NCT05807711 | Completed Phase 4

• 1 other identifier: 0107591
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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

Conditions

End Stage Renal Disease; Hypertension, Renal

Keywords

L-methylfolate; methylcobalamine; homocysteine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• myocardial infarction, stroke and cardiovascular events.

  3 months

Study Arms (2)

Experimental: Intervention group

ACTIVE COMPARATOR

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

No Intervention: Control group

NO INTERVENTION

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.

Interventions

L-Methyl Folate and methylcobalamine DRUG

Dietary supplement labeled to contain methylfolate 800 micrograms and methylcobalamine 1000 micrograms

Experimental: Intervention group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Faculty of Pharmacy, Alexandria University

Alexandria, Alexandria Governorate, 21521, Egypt

Location

Related Publications (5)

• 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.

  PMID: 18587236 BACKGROUND

• 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.

  PMID: 11562419 BACKGROUND

• 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.

  PMID: 15385656 BACKGROUND

• 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.

  PMID: 27847909 BACKGROUND

• Salem MS, Hamdy NA, Elghoneimy HA, El Gowelli HM. Efficacy of L-methylfolate and methylcobalamin in treating resistant hypertension associated with elevated serum homocysteine in hemodialysis patients. BMC Nephrol. 2026 Jan 24. doi: 10.1186/s12882-025-04726-8. Online ahead of print.

  PMID: 41580678 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Hypertension, Renal

Interventions

5-methyltetrahydrofolate; mecobalamin

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Hanan M El-gowelli, PhD

  Professor of Pharmacology & Toxicology, Alexandria University

  PRINCIPAL INVESTIGATOR

• Hesham A Elghoneimy, PhD

  Associate Professor of Internal Medicine, Alexandria University

  PRINCIPAL INVESTIGATOR

• Noha A Hamdy, PhD

  Associate Professor of Clinical Pharmacy, Alexandria University

  PRINCIPAL INVESTIGATOR

• Mohamed S Salem, PharmD

  Master's student in Clinical Pharmacy and Pharmacy Practice, Alexandria University.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label, single-center, randomized controlled trial

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 11, 2023
• Study Start: April 1, 2023
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: January 13, 2025

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)