The Vitamin K2 and D3 Intervention Trial in Children and Adolescents With the Low-energy Fractures

Rationale and Design of the Vitamin K2 and Vitamin D3 Intervention Trial in Children and Adolescents With the Low-energy Bone Fractures

a prospective, three- month, randomized, double-blind, placebo-controlled, intervention trial (RDBPC), investigating the effect of vitamin K2 (menaquinone-7) and vitamin D3 on the healing process of low-energy bone fractures in children and adolescents

Study Overview

• Status: Recruiting
• Conditions: Vitamin D3; Fracture Healing; Deficiency of Vitamin K2
• Intervention / Treatment: Dietary supplement: Vitamin D supplementation; Dietary supplement: Vitamin D and K2 supplementation; Dietary supplement: Placebo

Detailed Description

At the admission of patients to the orthopedic outpatient clinic, presence of low- energy fractures will be established based on the anamnesis, physical examination and radiological evaluation. Tests to obtain the baseline blood levels of vitamin D3 will be performed, and only children with vitamin D3 levels lower than 30ng/ml in the blood will be included in the study. The selected population will then be randomly assigned by an independent investigator to the three study groups, receiving daily for three months identical- looking soft gel capsules (1 capsule/patient/day) containing supplements of vitamin D3 2,000 IU, 90 mcg of vitamin K2 as menaquinone-7 combined with 2,000 IU D3, and olive oil-containing placebo capsules respectively. During the 3-month follow-up visits to the outpatient orthopedic clinic, the pediatric orthopedist will examine the patient, evaluate the X-ray, and determine the progress in bone union and the range of joint motion. The patients will visit the clinic on weeks 1,2,4,6,8, and 12. The compliance taking the supplements will be assessed by registering a pill count returned by a patient during the scheduled visit. The blood samples will be collected upon admission to the study, day 0, and after the 3-month regimen. The blood samples will be collected for evaluation of bone turnover markers and the status of vitamin K and vitamin D3. The primary evaluation endpoints will include: the dynamics of fracture healing, changes in levels of osteocalcin, and vitamin K and vitamin D3 levels against the placebo group. The bone fracture healing milestones will be based on bone union defined as the absence of pain and the presence of bridging callus in three of the four cortices seen on the front rear projection and lateral radiographic views of the bone. Delayed union is defined as incomplete consolidation at 90 Days

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michał Karpiński, MD; Phone Number: 48 692224714; Email: gufkarp@gmail.com

Study Locations

• Poland
  • Bialystok, Poland, 15-274
    • Recruiting
    • Department of Pediatric Orthopedics and Traumatology Medical University of Bialystok
    • Contact: Michal Karpinski, MD; Phone Number: +48 692224714; Email: gufkarp@gmail.com
    • Contact: Janusz Popko, MD, PhD; Phone Number: +48 857450895; Email: jpopko@umb.edu.pl
    • Principal Investigator: Michal Karpinski, MD
    • Principal Investigator: Janusz Popko, MD, PhD
    • Principal Investigator: Vladimir Badmaev, MD, PhD
    • Principal Investigator: Tomasz Guszczyn, MD, PhD
    • Sub-Investigator: Katarzyna Maresz, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age < 18 years
• Presence of low-energy fracture
• Vitamin D serum level <30ng/ml

Exclusion Criteria:

• Age > 18 years
• Lack of low-energy bone fracture
• Oral anticoagulants treatments, which interfere with vitamin K cycle
• Current supplementation with vitamin vitamins K2 or vitamin D3
• Osteogenesis imperfecta and other bone diseases
• Vitamin D concentration > 30ng/ml

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D group; vitamin D supplementation - time to fracture healing	Dietary supplement: Vitamin D supplementation; if supplementation of vitamin D alone changes the time to fracture healing
Active Comparator: Vitamin D and K2 group; Vitamin D and K 2 supplementation - time of fracture healing	Dietary supplement: Vitamin D and K2 supplementation; if supplementation of vitamin D and K2 changes the time to fracture healing
Placebo Comparator: Placebo group; Placebo - time to fracture healing	Dietary supplement: Placebo; Placebo control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to bone union	The bone fracture healing milestones will be based on bone union defined as the absence of pain and the presence of bridging callus in three of the four cortices seen on the AnteroPosteral and lateral radiographs	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D concentration changes	changes in vitamin D serum concentration	3 months
Vitamin K2 concentration changes	changes in vitamin K2 serum concentration	3 months
Changes in bone markers concentration	Changes in bone-specific alkaline phosphatase (BALP), N-terminal telopeptide (NTX)	3 months

Collaborators and Investigators

• Sponsor: Medical University of Bialystok
• Collaborators: Lomza State University of Applied Sciences; International Science & Health Foundation; American Medical Holdings Inc
• Investigators: Study Chair: Janusz Popko, MD, PhD, Faculty of Health Sciences; Principal Investigator: Michał Karpinski, MD, Department of Pediatric Orthopedics and Traumatology; Study Chair: Tomasz Guszczyn, MD, PhD, Department of Pediatric Orthopedics and Traumatology; Study Chair: Sylwia Chojnowska, PhD, Faculty of Health Sciences Lomza; Study Chair: Katarzyna Maresz, PhD, International Science &Health Foundation; Study Director: Vladimir Badmaev, American Medical Holdings Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Anticipated): December 24, 2022
• Study Completion (Anticipated): January 20, 2023

Study Registration Dates

• First Submitted: March 7, 2019
• First Submitted That Met QC Criteria: March 10, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: children; vitamin D; vitamin K2; fracture healing; low-energy fractures
• Additional Relevant MeSH Terms: Wounds and Injuries; Hematologic Diseases; Nutrition Disorders; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Blood Coagulation Disorders; Fractures, Bone; Vitamin K Deficiency; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: MUBialystok1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No