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Vitamin K2 Supplements for Muscle Recovery (Recovery)

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ClinicalTrials.gov Identifier: NCT05161975
Recruitment Status : Unknown
Verified November 2021 by Lithuanian Sports University.
Recruitment status was:  Not yet recruiting
First Posted : December 17, 2021
Last Update Posted : December 17, 2021
Sponsor:
Collaborators:
Kappa Bioscience AS
LSMU Kauno ligonine
Information provided by (Responsible Party):
Lithuanian Sports University

Study Description
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Brief Summary:
Ankle injury is one of the most common injuries which can have long term consequences. Ankle immobilization is often applied for up to six weeks to ensure healing of the soft tissue and fractured bones after such an injury. This causes significant wasting of the lower leg muscles driven by inflammation and oxidative stress. The rate of muscle atrophy and recovery after injury varies significantly by sex and age. These differences might be linked to changes in gene and protein expression associated with regulation of protein synthesis and proteolysis. Interventions that reduce the deleterious effects of ankle injury as well as understanding of the underlying mechanisms could be particularly useful in promotion of healthy ageing. Vitamin K includes a group of structurally related compounds. Phylloquinone (vitamin K1) and menaquinones (vitamin K2s) of which MK-4 and MK-7 are the most important. Vitamin K2 has anti-inflammatory and antioxidant effects and thus may be effective in reducing muscle atrophy during limb immobilization and improving recovery of muscle function after injury. This aim of the current study is to investigate if vitamin K2 supplements can ameliorate muscle atrophy and improve recovery of muscle function after ankle injury. The investigators will study younger (18-39 year old) and older (40-60 year old) men and women to assess effects of sex and age.

Condition or disease Intervention/treatment Phase
Muscle Atrophy Cachexia Dietary Supplement: Vitamin K2 Not Applicable

Detailed Description:

Muscle weakness is associated with impaired quality of life, increased risk of falling, disability and premature mortality. Whilst ageing results in a progressive decline, even short periods of low physical activity can result in significant deterioration of muscle function and metabolic health. One such period of very low activity can occur following illness or injury. This can lead to decrease in lower limb muscle mass and strength. Muscle exercise training promotes recovery of skeletal muscles after injury though improvements vary between individuals and appear to decrease with age. Strategies to retard loss of muscle mass and function during inactivity are, thus, of critical importance in understanding of the mechanisms underlying such effects.

Vitamin K includes a group of structurally related compounds named phylloquinone (vitamin K1) and menaquinones (vitamin K2s) of which MK-4 and MK-7 are the most important. Vitamin K is an essential cofactor for gamma carboxylation, required for the effective function of a range of proteins and has been linked to chronic disease and inflammation. Muscle cell studies suggest that vitamin K2 increases expression of myogenic transcription factors such as MyoD and promotes muscle cell proliferation. There are 20 described vitamin K dependent proteins (VKDPs). It is also known that vitamin K2 inhibits the activation of NFkB independently of gamma-carboxylation. This prevents nuclear entry of NFkB and therefore, consequently, vitamin K2 inhibits NFkB to interact with its nuclear receptors. In addition, Vitamin K2 can function as an electron carrier in mitochondria, and therefore play an inhibitory role on oxidative stress and release of ROS. There is, therefore, a strong rationale for investigating the effects of vitamin K2 during ankle immobilisation. The aim of the study is to investigate the effects of vitamin K2 on skeletal muscles after ankle injury and in the recovery process.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: We will carry out a double-blinded, randomized, placebo controlled clinical trial. We will recruit 18-60 years old men and women who have sustained ankle injury and arrived to LSMU Kauno ligonine for treatment. The volunteers will be randomly assigned to the vitamin K2 (MK-7, 330 micrograms) or placebo group. We expect to see 3-mm difference in muscle thickness between the groups. The gastrocnemius muscle thickness is reported to be 17.49 ± 3.81 mm (Kirmaci et al. 2021). Thus, 25 volunteers in each group are needed (statistical power = 80%, p < 0.05) for the study. We will recruit 30 volunteers into each group as some volunteers might drop out of the study. We will recruit equal number of 18-39 year old and 40-59 year olds into both groups (n =15 each) to minimize effects of age.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of Vitamin K2 Supplements on Recovery of Lower Limb Muscle Function After Ankle Injury in Adults
Estimated Study Start Date : December 15, 2021
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Menadione

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Food supplement tablets do not contain vitamin K2
 Dietary Supplement: Vitamin K2
Volunteers will be randomly assigned to vitamin K2 or placebo group and consume one tablet of the food supplement per day.
Experimental: Vitamin K2
Food supplement tablets contain vitamin K2
 Dietary Supplement: Vitamin K2
Volunteers will be randomly assigned to vitamin K2 or placebo group and consume one tablet of the food supplement per day.


Outcome Measures
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Primary Outcome Measures :
  1. Muscle thickness [ Time Frame: 12 weeks. ]
    Transverse images of medial and lateral gastrocnemius, soleus and tibialis anterior muscles will be obtained using B-mode ultrasonography with a 10-15 MHz transducer.

  2. Muscle strength [ Time Frame: 12 weeks. ]
    Plantar flexor and extensor strength will be measured using isokinetic dynamometer (Biodex System 3 Biodex Medical Systems, Inc., Shirley, NY, USA).

  3. Vitamin K2 status [ Time Frame: 12 weeks. ]
    Blood samples will be taken and plasma levels of vitamin K2 will be assessed.


Secondary Outcome Measures :
  1. Cytokine profile [ Time Frame: 12 weeks. ]
    Blood samples will be taken and ELISA assays for insulin, myostatin, TGF-β2, IGF-1, IL-1b, IL-6 and TNF-alpha will be performed

  2. Gene expression profile [ Time Frame: 12 weeks. ]
    Biopsies of soleus and gastrocnemius muscles will be taken. The mRNA levels of p62, Atrogin 1, MuRF 1, LC3b and Gapdh were assessed using SYBR Green (#4367659, Thermo Fisher Scientific) assay for quantitative PCR.

  3. Protein expression profile [ Time Frame: 12 weeks. ]
    Biopsies of soleus and gastrocnemius muscles will be taken. Western blotting will be carried to examine signalling pathways that control protein synthase (Akt-mTOR-p70s6k).

  4. Metabolic enzyme activity [ Time Frame: 12 weeks. ]
    Biopsies of soleus and gastrocnemius muscles will be taken. Enzyme assays for citrate synthase (CS), succinate dehydrogenase (SDH), β-hydroxyacyl-coenzyme dehydrogenase (HAD) and other metabolic enzyme will be carried out.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-60 years of age;
  • Lives in Lithuania;
  • Able and willing to give informed written consent to participate in the study;
  • Recent (24 h before volunteering for the study) ankle injury requiring 6-week ankle immobilization;
  • Exercise training program during 6-week recovery is recommended.

Exclusion Criteria:

  • Body mass index (BMI) is greater than 30 kg / m2;
  • Diabetes complicates cardiovascular diseases,
  • Liver disease;
  • Blood pressure is greater than 150/90mmHg during the first measurement;
  • Incidences of consciousness loss;
  • Cancer;
  • Dementia;
  • Other injuries that affect lower limb muscles;
  • Use of anticoagulant drugs;
  • Smoking;
  • Drug abuse;
  • Using drugs that affect muscle function (steroids).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05161975


Contacts
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Contact: Aivaras Ratkevicius, Dr. +37069009974 aivaras.ratkevicius@lsu.lt
Contact: Tomas Kadusauskas, M.D. tomas.kadusauskas@stud.lsu.lt

Locations
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Lithuania
Lithuanian Sports University
Kaunas, Lithuania, 44221
Contact: Aivaras Ratkevicius, Dr.    +37069009974    aivaras.ratkevicius@lsu.lt   
LSMU Kauno ligonine
Kaunas, Lithuania, 47144
Contact: Tomas Kadusauskas, M.D    +37069849471    tomas.kadusauskas@stud.lsu.lt   
Sponsors and Collaborators
Lithuanian Sports University
Kappa Bioscience AS
LSMU Kauno ligonine
Investigators
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Principal Investigator: Aivaras Ratkevicius, Dr. Lithuanian Sports University
More Information
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Publications:

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Responsible Party: Lithuanian Sports University
ClinicalTrials.gov Identifier: NCT05161975    
Other Study ID Numbers: LithuanianSportsU-7
First Posted: December 17, 2021    Key Record Dates
Last Update Posted: December 17, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lithuanian Sports University:
Cachexia; Insulin Resistance; Muscle Weakness; Exercise training
Additional relevant MeSH terms:
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Muscular Atrophy
Wasting Syndrome
Cachexia
Atrophy
Pathological Conditions, Anatomical
Weight Loss
Body Weight Changes
Body Weight
Thinness
Metabolic Diseases
Nutrition Disorders
Neuromuscular Manifestations
 Neurologic Manifestations
Nervous System Diseases
Vitamin K
Vitamin K 2
Vitamins
Micronutrients
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants