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Vitamin K2 Supplements for Muscle Recovery

Sponsor
Lithuanian Sports University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05161975
Collaborator
Kappa Bioscience AS (Other), LSMU Kauno ligonine (Other)
60
Enrollment
2
Locations
2
Arms
24.5
Anticipated Duration (Months)
30
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

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
  • Dietary Supplement: Vitamin K2
 N/A

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

Study Type:
Interventional
Anticipated 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.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
Anticipated Study Start Date :
Dec 15, 2021
Anticipated Primary Completion Date :
Oct 31, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

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

Primary Outcome Measures

  1. Muscle thickness [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 [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 [12 weeks.]

    Blood samples will be taken and plasma levels of vitamin K2 will be assessed.

Secondary Outcome Measures

  1. Cytokine profile [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 [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 [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 [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

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Locations

Site City State Country Postal Code
1 Lithuanian Sports University Kaunas Lithuania 44221
2 LSMU Kauno ligonine Kaunas Lithuania 47144

Sponsors and Collaborators

  • Lithuanian Sports University
  • Kappa Bioscience AS
  • LSMU Kauno ligonine

Investigators

  • Principal Investigator: Aivaras Ratkevicius, Dr., Lithuanian Sports University

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Lithuanian Sports University
ClinicalTrials.gov Identifier:
NCT05161975
Other Study ID Numbers:
  • LithuanianSportsU-7
First Posted:
Dec 17, 2021
Last Update Posted:
Dec 17, 2021
Last Verified:
Nov 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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:
Muscular Atrophy
Wasting Syndrome
Cachexia
Vitamin K
Vitamin K 2

Study Results

No Results Posted as of Dec 17, 2021