Clinical trial NCT05547750: Effect of Vitamin K2 in the Treatment of Nocturnal Leg Cramps in Older Population
Official title: Effect of Vitamin K2 in the Treatment of Nocturnal Leg Cramps in Older Population: Study Protocol of a Randomized, Double-blind, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nocturnal Leg Cramps
Keywords: Nocturnal Leg Cramps
Vitamin K2
older population
Lead sponsor: The Third People's Hospital of Chengdu
Sponsor class: OTHER
Collaborators: name: Afﬁliated Hospital of North Sichuan Medical College
First posted: 2022-09-21
Enrollment: 200
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Nocturnal leg cramps (NLCs) are sudden contractions of the leg muscles, usually in the posterior calf muscles at night, affecting sleep quality. Because the precise pathophysiology of NCLs is unclear, different interventions have been proposed. There is conflicting evidence regarding the efficacy of conventional interventions in preventing cramps. Thus, the present study aims to investigate the effects of vitamin K2 for NLCs in a prospective randomized, double-blind, controlled trial.

Detailed description: Nocturnal leg cramps (NLCs) are spontaneous contractions of muscles. The gastrocnemius is commonly involved, lasting from a few seconds to a few minutes. Patients might wake up with pain during attacks, making it difficult to sleep for a short period. It commonly occurs \>60-year-old. The medical history and physical examination are usually sufficient to differentiate nocturnal leg cramps from other conditions, such as restless legs syndrome, claudication, myositis, and peripheral neuropathy. Factors that may lead to leg cramps attacks include hemodialysis, electrolyte imbalance, metabolic disorders, and congenital disorders. The cramps can be relieved by passive stretching of the gastrocnemius and deep tissue massage, but such prevention is limited, especially in patients with refractory muscle cramps. Quinine has been shown to be effective in treating NLCs but is not recommended by the US Food and Drug Administration due to severe side effects. Magnesium supplements are often used as a preventative treatment for NLCs; however, their effectiveness is controversial. Magnesium supplements are widely marketed for the prophylaxis of NLCs since a double-blind, placebo-controlled study proved their effectiveness in pregnant women. However, magnesium administration did not show significant benefits in NLCs in double-blind, placebo-controlled studies. Meta-analysis of some randomized control trials (RCTs) showed that magnesium therapy did not appear to be effective in the treatment of NLCs in the general population, but may have a negligible effect in pregnant women. Therefore, seeking new approaches to manage NLCs is imperative.

Vitamin K is a fat-soluble vitamin involved in carboxylation and activating several dependent proteins. It is found in two isoforms (phylloquinone (vitamin K1) and menaquinone (vitamin K2)) that differ in length and degree of saturation of the side chain. In addition to their role in coagulation, vitamin K-dependent proteins are involved in vascular calcification and osteoporosis physiology. Accumulating evidence has shown the beneficial effects of vitamin K2 supplementation on cardiovascular and bone health.

Another study revealed that vitamin K3 relieved muscle cramps by effectuating the voltage-dependent calcium channels to release the calcium stored in the cells, thus reducing the frequency of muscular contractions. To the best of our knowledge, no study has yet investigated the efficacy of vitamin K in NLCs. In addition, vitamin K2 has a good safety profile compared to other medications. Our pilot study demonstrated that vitamin K2 supplementation decreases the frequency, duration, and severity of muscle cramps in hemodialysis patients. To further investigate the efficacy and safety of vitamin K2 in NLCs, we designed this prospective, multicenter, randomized, double-blind trial.

Eligibility criteria: Inclusion Criteria:

1. Unexplained cramps occurred two or more times in 2 weeks.
2. Age ≥65-year-old.

Exclusion criteria

1. Cramps caused by specific metabolic diseases and specific neuropathies (hypothyroidism, hemodialysis, hypoglycemia, alcoholism, amyotrophic lateral sclerosis, and poliomyelitis complications, lumbar spinal stenosis, Parkinson's disease, radiculopathies, and motor neuron diseases);
2. Suffering from malignant tumors (breast cancer, prostate cancer, lymphoma, and multiple myeloma);
3. Taking diuretics, or vitamin K antagonist;
4. Taking supplements with vitamin K2 within 2 months before enrollment;

Primary outcomes:
measure: The number of NLCs attacks
timeFrame: Comparing frequency differences between vitamin K2 and placebo treatment phases of NLCs in a 8 weeks investigation
Secondary outcomes:
measure: The duration of NLCs
timeFrame: During the 8 weeks of investigation, the differences in the duration during NLCs attacks will record in the trial compared to vitamin K2- and placebo-treated arms
measure: The severity of NLCs
timeFrame: During the 8 weeks of investigation, pain severity during NLCs attacks is recorded in the trial and compared to vitamin K2- and placebo-treated arms
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Chengdu Third People's Hospital
state: Sichuan
Study officials:
References: