Nocturnal Leg CrampsNCT05547750
Effect of Vitamin K2 in the Treatment of Nocturnal Leg Cramps in Older Population
A study testing Vitamin K2 in people with Nocturnal Leg Cramps, run by The Third People's Hospital of Chengdu at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Nocturnal Leg Cramps
- What is being tested?
- Vitamin K2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2022to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Unexplained cramps occurred two or more times in 2 weeks.
- Age ≥65-year-old.
Who cannot join
- 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);
- Suffering from malignant tumors (breast cancer, prostate cancer, lymphoma, and multiple myeloma);
- Taking diuretics, or vitamin K antagonist;
- Taking supplements with vitamin K2 within 2 months before enrollment;
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Nocturnal Leg Cramps
- Being tested
- Vitamin K2, Placebo
- Keywords
- Nocturnal Leg Cramps, Vitamin K2, older population
- Medical subject headings
- Sleep-Wake Transition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin K2Drug
Vitamin K2 is a fat-soluble and one of the body's indispensable vitamins. It is mainly synthesized by gut bacteria in the body and plays a role in the mitochondrial electron transport chain. It boosts calcium metabolism, acts on osteoblasts, and promotes bone tissue calcification. It also inhibits osteoclasts from causing bone resorption, thus increasing bone density, and preventing osteoporosis. Furthermore, it regulates the use of calcium and promotes the inhibition of vascular calcification by matrix Gla protein (MGP) activity. Vitamin K2 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' activity. It does not enhance the carboxylation of prothrombin in healthy individuals. Vitamin K2 administration does not alter the hemostatic balance in healthy populations without anticoagulation treatment. Thus, vitamin K2 is deemed to have a good safety profile.
PlaceboDrug
Similar-looking placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| vitamin K2 arm | Experimental | The vitamin K2 arm takes vitamin K2 180 μg/day at bedtime for 8 weeks. Receives: Drug: Vitamin K2 |
| Placebo | Placebo comparator | The placebo group takes a placebo at bedtime for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of NLCs attacks
The mean number of NLC attacks per week
Measured: Comparing frequency differences between vitamin K2 and placebo treatment phases of NLCs in a 8 weeks investigation
Secondary outcomes (2)
The duration of NLCs
Duration of muscle cramps in minutes
Measured: 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
The severity of NLCs
The severity of muscle cramps using a 1-10 analog scale（1-3 points, mild pain, tolerable, does not affect sleep; 4-6 points, moderate pain, affects sleep, also tolerable; 7-10 points, sharp pain, intolerable.）
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start1 Oct 2022
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nocturnal Leg CrampsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Third People's Hospital of Chengdu
- Sponsor type
- University, hospital or other
- Collaborators
- Affiliated Hospital of North Sichuan Medical College
- Responsible party
- Principal investigator, Ying Li, The Third People's Hospital of Chengdu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05547750
- Sponsor's protocol ID
- 2022-S17
- Status last verified
- Jan 2025
- First submitted
- 15 Sep 2022
- Last updated
- 17 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tan J, Zhu R, Li Y, Wang L, Liao S, Cheng L, Mao L, Jing D. Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA Intern Med. 2024 Dec 1;184(12):1443-1447. doi: 10.1001/jamainternmed.2024.5726.
PubMed 39466236Li Y, Zhu R, Wang L, Tan J. Effect of vitamin K2 in the treatment of nocturnal leg cramps in the older population: Study protocol of a randomized, double-blind, controlled trial. Front Nutr. 2023 Feb 23;10:1119233. doi: 10.3389/fnut.2023.1119233. eCollection 2023.
PubMed 36908924
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05547750
- Acronym / sponsor ID
- 2022-S17
- Conditions
- Nocturnal Leg Cramps
- Keywords
- Nocturnal Leg Cramps, Vitamin K2, older population
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- The Third People's Hospital of ChengduUniversity, hospital or other
- Collaborators
- Affiliated Hospital of North Sichuan Medical College
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 21 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vitamin K2 arm | Experimental | Drug: Vitamin K2The vitamin K2 arm takes vitamin K2 180 μg/day at bedtime for 8 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo group takes a placebo at bedtime for 8 weeks. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Unexplained cramps occurred two or more times in 2 weeks.
- Age ≥65-year-old.
Key exclusion criteria (4 listed)
- 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);
- Suffering from malignant tumors (breast cancer, prostate cancer, lymphoma, and multiple myeloma);
- Taking diuretics, or vitamin K antagonist;
- Taking supplements with vitamin K2 within 2 months before enrollment;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin K2Vitamin K2 is a fat-soluble and one of the body's indispensable vitamins. It is mainly synthesized by gut bacteria in the body and plays a role in the mitochondrial electron transport chain. It boosts calcium metabolism, acts on osteoblasts, and promotes bone tissue calcification. It also inhibits osteoclasts from causing bone resorption, thus increasing bone density, and preventing osteoporosis. Furthermore, it regulates the use of calcium and promotes the inhibition of vascular calcification by matrix Gla protein (MGP) activity. Vitamin K2 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' activity. It does not enhance the carboxylation of prothrombin in healthy individuals. Vitamin K2 administration does not alter the hemostatic balance in healthy populations without anticoagulation treatment. Thus, vitamin K2 is deemed to have a good safety profile. | Drug | vitamin K2 arm |
| PlaceboSimilar-looking placebo tablets | Drug | Placebo |
Primary outcome
The number of NLCs attacks
Time frame: Comparing frequency differences between vitamin K2 and placebo treatment phases of NLCs in a 8 weeks investigation
The mean number of NLC attacks per week
2 secondary outcomes
The duration of NLCs
Time frame: 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
The severity of NLCs
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2025.
- Derived from this study: PubMed 39466236Tan J, Zhu R, Li Y, Wang L, Liao S, Cheng L, Mao L, Jing D. Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA Intern Med. 2024 Dec 1;184(12):1443-1447. doi: 10.1001/jamainternmed.2024.5726.
- Derived from this study: PubMed 36908924Li Y, Zhu R, Wang L, Tan J. Effect of vitamin K2 in the treatment of nocturnal leg cramps in the older population: Study protocol of a randomized, double-blind, controlled trial. Front Nutr. 2023 Feb 23;10:1119233. doi: 10.3389/fnut.2023.1119233. eCollection 2023.
- Individual participant dataSharing planned: No
Related trials for Nocturnal Leg Cramps
Recruiting
The Effect of a Daily Magnesium and Melatonin Supplement on Sleep Quality in People With Nighttime Leg Cramps
Poor Sleep Quality, Leg Cramps, Nocturnal
Not yet recruiting
Weighted Blanket in Pregnancy
Leg Cramps, Nocturnal, Poor Sleep Quality
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin K2 in people with Nocturnal Leg Cramps, run by The Third People's Hospital of Chengdu at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of NLCs attacks (time frame: Comparing frequency differences between vitamin K2 and placebo treatment phases of NLCs in a 8 weeks investigation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05547750, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2025.