Clinical trial NCT05161975: Vitamin K2 Supplements for Muscle Recovery
Official title: Effects of Vitamin K2 Supplements on Recovery of Lower Limb Muscle Function After Ankle Injury in Adults
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Muscle Atrophy
Cachexia
Keywords: Cachexia; Insulin Resistance; Muscle Weakness; Exercise training
Lead sponsor: Lithuanian Sports University
Sponsor class: OTHER
Collaborators: name: Kappa Bioscience AS
name: LSMU Kauno ligonine
First posted: 2021-12-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

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.

Eligibility 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).

Primary outcomes:
measure: Muscle thickness
timeFrame: 12 weeks.
measure: Muscle strength
timeFrame: 12 weeks.
measure: Vitamin K2 status
timeFrame: 12 weeks.
Secondary outcomes:
measure: Cytokine profile
timeFrame: 12 weeks.
measure: Gene expression profile
timeFrame: 12 weeks.
measure: Protein expression profile
timeFrame: 12 weeks.
measure: Metabolic enzyme activity
timeFrame: 12 weeks.
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Lithuanian Sports University
city: Kaunas
country: Lithuania
facility: LSMU Kauno ligonine
Study officials:
affiliation: Lithuanian Sports University
name: Aivaras Ratkevicius, Dr.
role: PRINCIPAL_INVESTIGATOR
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