Role of Vitamin K2 in Chronic Kidney Disease

NCT05942053 | Recruiting Phase 4

• 1 other identifier: Vitamin K2 in CKD
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized placebo controlled double blind parallel clinical study will be conducted on 44 non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b).Clinical Study Evaluating the Role of Vitamin K2 as Adjuvant Therapy to Angiotensin Converting Enzyme Inhibitor on Blood Pressure, Proteinuria and Bone Metabolism in Patients with Chronic Kidney Disease. Patients will be recruited from, Internal Medicine Department, Nephrology Unit, Alexandria Main University Hospital, Egypt. Patients with albumin-to-creatinine ratio ≥ 30 mg/g, with serum Potassium \< 5 mEq/L and newly diagnosed patients with hypertension. The study duration will be 6 months. The patients will be randomized using stratified random block method into two groups. Group 1: Control group Non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b). Patients will be treated with ramipril 10 mg/day and a placebo match vitamin K2 capsules once per day.The dose of ramipril may be modified according to blood pressure control. Group 2: Vitamin K2 (menaquinone-7) Non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b).Patients will be treated with ramipril 10 mg/day and vitamin K2 capsules (menaquinone-7) 90 mcg/day. The dose of ramipril may be modified according to blood pressure control. Participants will be followed-up by weekly telephone calls and monthly direct meetings to assess their adherence for 6 months.

Conditions

Chronic Kidney Diseases

Keywords

Proteinuria, Bone Metabolism, Vitamin K2

Outcome Measures

Primary Outcomes (7)

• The change in kidney function test measured by creatinine clearance (eGFR) mL/min/1.73m2 which will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, 2021

  Assessment of kidney functions at baseline, 4 weeks, 3 and 6 months after initiation of ACEI by assessment: Estimated glomerular filtration rate (eGFR) in mL/min/1.73m2 which will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, 2021.

  The study duration will be 6 months

• The change in proteinuria level be assessed using Albumin-to-creatinine ratio (ACR) ratio (mg/g)

  Assessment of Proteinuria at the time of enrollment, 3 and 6 months after intervention. Albumin-to-creatinine ratio will be calculated by dividing the urinary albumin concentration by the urinary creatinine concentration (mg/g)

  The study duration will be 6 months

• The change in blood pressure (mmHg) will be done using a mercury sphygmomanometer

  Measurement of blood pressure will be done using a mercury sphygmomanometer in accordance with recommendations of the American Heart Association and standardized office blood pressure measurements. The mean values of the duplicate measurements will be recorded. The blood pressure will be assessed at baseline and every 4 weeks.

  The study duration will be 6 months

• The change in Blood urea nitrogen (BUN) (mg/dl)

  Assessment of BUN (mg/dl) at baseline, 4 weeks, 3 and 6 months after initiation of ACEI

  The study duration will be 6 months

• The change in serum potassium (meq/l).

  Assessment of serum potassium (meq/l) at baseline, 4 weeks, 3 and 6 months after initiation of ACEI

  The study duration will be 6 months

• The change in serum creatinine (mg/dl)

  Assessment of serum creatinine (mg/dl) at baseline, 4 weeks, 3 and 6 months after initiation of ACEI

  The study duration will be 6 months

• The change in serum urea (mg/dl)

  Assessment of serum urea (mg/dl) at baseline, 4 weeks, 3 and 6 months after initiation of ACEI

  The study duration will be 6 months

Secondary Outcomes (6)

• The change in chronic kidney disease-mineral and bone disorder related parameters by assessment Serum level of Fibroblast growth factor-23 (FGF-23) (pg/ml)

  The study duration will be 6 months.

• The change in I-PTH (pg/ml)

  The study duration will be 6 months.

• The change in vitamin D level (ng/ml)

  The study duration will be 6 months.

• The change in serum calcium level (mg/dl)

  The study duration will be 6 months.

• The change in serum phosphorus level (mg/dl)

  The study duration will be 6 months.

Study Arms (2)

Group 1: Control group

PLACEBO COMPARATOR

Non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b). Patients will be treated with ramipril 10 mg/day and a placebo match vitamin K2 capsules once per day. The dose of ramipril may be modified according to blood pressure control. Participants will be followed-up by weekly telephone calls and monthly direct meetings to assess their adherence for 6 months.

Drug: Placebo

Vitamin K2 (menaquinone-7)

ACTIVE COMPARATOR

Non-dialysis chronic kidney disease (CKD) patients (Stages 2-3b).Patients will be treated with ramipril 10 mg/day and vitamin K2 capsules (menaquinone-7) 90 mcg/day. The dose of ramipril may be modified according to blood pressure control. Participants will be followed-up by weekly telephone calls and monthly direct meetings to assess their adherence for 6 months.

Drug: Vitamin K 2

Interventions

Placebo DRUG

Placebo match vitamin K2 capsules once per day.

Group 1: Control group

Vitamin K 2 DRUG

Patients will be treated with vitamin K2 (menaquinone-7) 90 mcg/day.

Also known as: menaquinone-7

Vitamin K2 (menaquinone-7)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Both sexes.
• Patients matched in the duration of CKD.
• Non-dialysis chronic kidney disease (CKD) patient with estimated glomerular filtration rate (GFR) 30-89 mL/min/1.73m2 (Stage 2-3b).
• Patients with albumin-to-creatinine ratio ≥ 30 mg/g.
• Patients with serum Potassium \< 5 mEq/L.
• A newly diagnosed patients with hypertension.

You may not qualify if:

• Patients with elevated level of potassium ≥ 5 mEq/L.
• Patients with diabetes.
• Patients with cancer.
• Patients with heart disease.
• Patients with hepato-biliary disease and other liver diseases.
• Patients with kidney stones and urinary tract infection.
• Patients with an overactive thyroid gland.
• Patients with bleeding disorder.
• History of drug allergy to ACEI or ARBs.
• Pregnant and breastfeeding women.
• Patients with blood pressure ≥180/110 or \<100/60.
• Patients on alteplase, azothiopurine, everolimus, sirolimus, lithium, non-steroidal anti-inflammatory drugs (epifenac, tenoxicam, Celecoxib….), potassium retentive diuretics (amiloride, spironolactone), other ACEIs and ARBs will be excluded to avoid possible drug-drug interactions with ramipril.
• Patients on omega-3 fatty acids; vitamins (especially A, C, E, K), Chemotherapy and oral anticoagulant (warfarin), cholestyramine, orlistate will be excluded to avoid possible drug interactions that could affect vitamin K2

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Faculty of Pharmacy Tanta University

Tanta, Capital of Gharbia Governorate., 31527, Egypt

RECRUITING

Related Publications (8)

• Liu TH, Tao WC, Liang QE, Tu WQ, Xiao Y, Chen LG. Gut Microbiota-Related Evidence Provides New Insights Into the Association Between Activating Transcription Factor 4 and Development of Salt-Induced Hypertension in Mice. Front Cell Dev Biol. 2020 Nov 13;8:585995. doi: 10.3389/fcell.2020.585995. eCollection 2020.

  PMID: 33282868 BACKGROUND

• Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL. Vitamins K and D status in stages 3-5 chronic kidney disease. Clin J Am Soc Nephrol. 2010 Apr;5(4):590-7. doi: 10.2215/CJN.06420909. Epub 2010 Feb 18.

  PMID: 20167683 BACKGROUND

• Fusaro M, Gallieni M, Porta C, Nickolas TL, Khairallah P. Vitamin K effects in human health: new insights beyond bone and cardiovascular health. J Nephrol. 2020 Apr;33(2):239-249. doi: 10.1007/s40620-019-00685-0. Epub 2019 Dec 19.

  PMID: 31858448 BACKGROUND

• Reardon LC, Macpherson DS. Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry? Arch Intern Med. 1998 Jan 12;158(1):26-32. doi: 10.1001/archinte.158.1.26.

  PMID: 9437375 BACKGROUND

• Dai B, David V, Martin A, Huang J, Li H, Jiao Y, Gu W, Quarles LD. A comparative transcriptome analysis identifying FGF23 regulated genes in the kidney of a mouse CKD model. PLoS One. 2012;7(9):e44161. doi: 10.1371/journal.pone.0044161. Epub 2012 Sep 6.

  PMID: 22970174 BACKGROUND

• Shane E, Mancini D, Aaronson K, Silverberg SJ, Seibel MJ, Addesso V, McMahon DJ. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med. 1997 Sep;103(3):197-207. doi: 10.1016/s0002-9343(97)00142-3.

  PMID: 9316552 BACKGROUND

• Rodriguez-Garcia M, Gomez-Alonso C, Naves-Diaz M, Diaz-Lopez JB, Diaz-Corte C, Cannata-Andia JB; Asturias Study Group. Vascular calcifications, vertebral fractures and mortality in haemodialysis patients. Nephrol Dial Transplant. 2009 Jan;24(1):239-46. doi: 10.1093/ndt/gfn466. Epub 2008 Aug 25.

  PMID: 18725376 BACKGROUND

• Ix JH, Katz R, Kestenbaum BR, de Boer IH, Chonchol M, Mukamal KJ, Rifkin D, Siscovick DS, Sarnak MJ, Shlipak MG. Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study). J Am Coll Cardiol. 2012 Jul 17;60(3):200-7. doi: 10.1016/j.jacc.2012.03.040. Epub 2012 Jun 13.

  PMID: 22703926 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Proteinuria

Interventions

Vitamin K 2; menaquinone 7

Condition Hierarchy (Ancestors)

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; Urination Disorders; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Officials

• Tarek Mostafa, PhD

  Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt, 31527

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dina Abdel Hamid, Masters

CONTACT

+2001020198970; pg_87899@pharm.tanta.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist

Study Record Dates

• First Submitted: June 26, 2023
• First Posted: July 12, 2023
• Study Start: July 15, 2023
• Primary Completion (Estimated): July 14, 2026
• Study Completion (Estimated): July 15, 2026
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)