Ligament InjuryNCT03747198
Methylsulfonylmethane on Knee Laxity
A study testing methylsulfonylmethane in people with Ligament Injury and Ligament; Laxity, run by University of California, Davis at 1 site in United States.
Trial summary
The proposed research will focus on determining the effect of methylsulfonylmethane (MSM) on knee laxity changes through the menstrual cycle in young active females. As an extension to recent discovery, that MSM reverses the negative effect of estrogen on engineered ligament function, the proposed work is designed to… Read more about this study
- Who is it for?
- Ages 18 to 30 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Ligament Injury, Ligament; Laxity, Tendon Rupture
- What is being tested?
- methylsulfonylmethane
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2019to 1 Oct 2019
- 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 18 to 30 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- • Regular menstrual cycle (~1 x month)
- Not using oral contraceptive
- No history of serious knee injury (e.g. ACL rupture)
- Not currently pregnant (known)
- Not routinely taking medication or supplements that would interact with study measures or be contraindicated (e.g. steroid injections)
Who cannot join
- • Irregular menstrual cycling (1 x month)
- Using oral contraceptive
- History of serious knee injury (e.g. ACL rupture)
- Currently pregnant or potential of being pregnant
- Routinely taking medication or supplements that would interact with study measures or be contraindicated (e.g. steroid injections)
Trial locations and contacts
1 site in 1 country.
United States1 site
Neurobiology, Physiology & Behaviour
Davis, California, 95616
About this study
Official title: The Effects of Methylsulfonylmethane on Knee Laxity in Active Young Females
The proposed research will focus on determining the effect of methylsulfonylmethane (MSM) on knee laxity changes through the menstrual cycle in young active females.
As an extension to recent discovery, that MSM reverses the negative effect of estrogen on engineered ligament function, the proposed work is designed to determine whether MSM can decrease the negative effect of estrogen on knee laxity in females.
Read more
Ligament function is determined by the content and cross-linking of collagen, which is influenced by a milieu of biochemical and mechanical parameters. The greater the amount and cross-linking the greater the stiffness and strength of these connective tissues. In engineered ligaments it has been previously shown that the high levels of estrogen, normally present in the days before and after ovulation, can inhibit the cross-linking enzyme lysyl oxidase. This decrease in collagen cross-linking likely increases connective tissue laxity and contributes to observed 4-fold greater occurrence of anterior cruciate ligament (ACL) rupture in females. Conversely, MSM increases collagen cross-linking and recent work conducted by the Baar lab in engineered human ligaments treated with high estrogen demonstrated that MSM could completely reverse the effects of estrogen on ligament mechanics.
The proposed research aims to advance this promising pre-clinical data and apply in a clinical trial. This research also proposes to quantify that knee laxity increases up to 5mm between the first day of menstruation and the day after ovulation and also that the magnitude of the increase in laxity is directly related to the magnitude of the change in estrogen. Importantly, a direct relationship between knee laxity and ACL rupture exists. For every 1.3mm increase in anterior-posterior knee displacement, the odds of ACL rupture increase 4-fold. Therefore, any treatment that decreases knee laxity could be expected to reduce ACL ruptures and have widespread application across the general active population and high-level athletics.
Read the detailed description
Familiarization: Subjects would come to the Human Performance lab for a study orientation to be informed of the goals of the study, have anthropometric data collected (InBody770, In Body, Cerritos, CA) and familiarized with all testing and data collection tools. The purpose of this is to collect anthropometric data, review the study procedures and study requirements.
Determination of menstruation date: After study familiarization instructions will be given to contact the research team and come back to the lab on the first day of menstruation to establish the individual study timeline. An ovulation kit will be provided. The ovulation kit would then be started at the end of the first reported menstrual cycle and be used daily until the 2-4 days of high estrogen (ovulation) are established.
Baseline data: After menstruation date is established, for the first two months of the study, subjects would come to the lab on the first day of menstruation and the day after ovulation, have their knee laxity measured (GNRB dynamic laximeter, Prothia, Worcester, MA) and salivary analysis to determine estrogen levels. The first two months would determine normal changes in knee laxity and estrogen levels throughout the cycle within each subject.
Intervention: Following the second ovulation testing day and once baseline values are established, subjects would be provided with 3 months of MSM or placebo control (rice flour) and instructed to take 2g each morning for the subsequent 3 months. Month 3 would serve as an MSM loading month and subjects would return to the laboratory throughout months 4 and 5 (day 14 and first day of menstruation) for mechanical and estrogen testing.
MSM or placebo treatments: The study will be a randomized double-blinded placebo-controlled trial. MSM or placebo capsules would be provided in a double blinded manner following the second mechanical test. Each individual would consume 2g of either the MSM or placebo control for the remainder of the study.
Intervention Product and Preparation Intervention: MSM (OptiMSM®) is a pure, generally recognized as safe (GRAS) designated product. MSM can be found in small amounts in corn, tomatoes, tea, coffee, milk.
Placebo: Rice flour is a commonly ingested food or additive. Intervention and placebo will be encapsulated in 1g vegetarian capsules (Hypromellose Capsule).
Both intervention and placebo capsules are identically transparent with white powder inside. Capsules containers with 805 capsules (2g per day for each month plus extra) will be prepared, packaged by Bergstrom nutrition and transported with blinded code (A or B) so only individuals responsible for intervention and placebo preparation are removed from conducting the study and are off site (Vancouver, Washington).
Product will be labelled by Bergstrom Nutrition. Subject ID and month (3, 4, or 5) will be filled in manually by University of California, Davis researcher upon randomization.
Determination of knee laxity: Knee laxity will be determined using a GNRB dynamic laximeter following established protocols. Briefly, with the femur held in place, a controlled pressure will be applied to the calf. The pressure increases from 0 to 200 Newtons and a sensor measures kneecap displacement (laxity) in millimeters.
Determination of estrogen levels: Salivary samples will be taken on the first day of menstruation and one day following ovulation for the 4 months of testing (month 1, 2, 4, 5). Estradiol levels in the saliva will be determined using the Estradiol Saliva ELISA kit (Rocky Mountain Diagnostics, CO) as per manufacturer's instructions.
Data Collected:
- Record of menstrual cycle
- Salivary estradiol levels as described above
- Measurements of knee laxity
- Conditions
- Ligament Injury, Ligament; Laxity, Tendon Rupture, Tendon Injuries
- Being tested
- methylsulfonylmethane, Placebo
- Medical subject headings
- Joint Instability, Tendon Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methylsulfonylmethaneDietary supplement
Also called MSM
Subjects will be given 2 g/day methylsulfonylmethane.
PlaceboOther
Subjects will be given 2 g/day placebo (rice flour).
| Study group | Role | What they receive |
|---|---|---|
| methylsulfonylmethane | Experimental | Subjects will be given 2 g/day of methylsulfonylmethane (MSM). Salivary estrogen will be measured around ovulation and menstruation each month for 3 months. Knee laxity will be measures 2 times per month at the same time points (ovulation, menstruation). Receives: Dietary Supplement: methylsulfonylmethane |
| Placebo | Placebo comparator | Subjects will be given 2 g/day placebo (rice flour). Salivary estrogen will be measured around ovulation and menstruation each month for 3 months. Knee laxity will be measures 2 times per month at the same time points as the intervention arm (ovulation, menstruation). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kneecap displacement (i.e. knee laxity)
Knee laxity will be measured at months 4 and 5 after the 3-month intervention period of the study. The measurement will be made in millimeters using a specially designed GNRB arthrometer, which is a computerized and automatic medical device developed and validated by Genourob.
Measured: 5 months
Secondary outcomes (3)
Weight
The subjects weight (kg) will be commented at the start of the study for subject demographic purposes. Measurements will be made with the InBody 570 Body Composition analyzer.
Measured: 1 day
Height
The subjects height (cm) will be commented at the start of the study for subject demographic purposes. Measurements will be made with a stadiometer.
Measured: 1 day
Body composition
The subjects body composition (% body fat) will be commented at the start of the study for subject demographic purposes. Measurements will be made with the InBody 570 Body Composition analyzer.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2018
- Study start1 Feb 2019
- Primary completion1 Oct 2019
- Study completion1 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ligament InjuryStudies 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blinded randomized parallel design
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Bergstrom Nutrition
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03747198
- Sponsor's protocol ID
- 1356922
- Status last verified
- May 2020
- First submitted
- 9 Nov 2018
- Last updated
- 1 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Methylsulfonylmethane on Knee Laxity in Active Young Females
- ClinicalTrials.gov ID
- NCT03747198
- Acronym / sponsor ID
- 1356922
- Conditions
- Ligament Injury, Ligament; Laxity, Tendon Rupture, Tendon Injuries
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Bergstrom Nutrition
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 Oct 2019 (actual)
- First posted
- 20 Nov 2018 (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.
The proposed research will focus on determining the effect of methylsulfonylmethane (MSM) on knee laxity changes through the menstrual cycle in young active females.
As an extension to recent discovery, that MSM reverses the negative effect of estrogen on engineered ligament function, the proposed work is designed to determine whether MSM can decrease the negative effect of estrogen on knee laxity in females.
Ligament function is determined by the content and cross-linking of collagen, which is influenced by a milieu of biochemical and mechanical parameters. The greater the amount and cross-linking the greater the stiffness and strength of these connective tissues. In engineered ligaments it has been previously shown that the high levels of estrogen, normally present in the days before and after ovulation, can inhibit the cross-linking enzyme lysyl oxidase. This decrease in collagen cross-linking likely increases connective tissue laxity and contributes to observed 4-fold greater occurrence of anterior cruciate ligament (ACL) rupture in females. Conversely, MSM increases collagen cross-linking and recent work conducted by the Baar lab in engineered human ligaments treated with high estrogen demonstrated that MSM could completely reverse the effects of estrogen on ligament mechanics.
The proposed research aims to advance this promising pre-clinical data and apply in a clinical trial. This research also proposes to quantify that knee laxity increases up to 5mm between the first day of menstruation and the day after ovulation and also that the magnitude of the increase in laxity is directly related to the magnitude of the change in estrogen. Importantly, a direct relationship between knee laxity and ACL rupture exists. For every 1.3mm increase in anterior-posterior knee displacement, the odds of ACL rupture increase 4-fold. Therefore, any treatment that decreases knee laxity could be expected to reduce ACL ruptures and have widespread application across the general active population and high-level athletics.
Detailed description
Familiarization: Subjects would come to the Human Performance lab for a study orientation to be informed of the goals of the study, have anthropometric data collected (InBody770, In Body, Cerritos, CA) and familiarized with all testing and data collection tools. The purpose of this is to collect anthropometric data, review the study procedures and study requirements.
Determination of menstruation date: After study familiarization instructions will be given to contact the research team and come back to the lab on the first day of menstruation to establish the individual study timeline. An ovulation kit will be provided. The ovulation kit would then be started at the end of the first reported menstrual cycle and be used daily until the 2-4 days of high estrogen (ovulation) are established.
Baseline data: After menstruation date is established, for the first two months of the study, subjects would come to the lab on the first day of menstruation and the day after ovulation, have their knee laxity measured (GNRB dynamic laximeter, Prothia, Worcester, MA) and salivary analysis to determine estrogen levels. The first two months would determine normal changes in knee laxity and estrogen levels throughout the cycle within each subject.
Intervention: Following the second ovulation testing day and once baseline values are established, subjects would be provided with 3 months of MSM or placebo control (rice flour) and instructed to take 2g each morning for the subsequent 3 months. Month 3 would serve as an MSM loading month and subjects would return to the laboratory throughout months 4 and 5 (day 14 and first day of menstruation) for mechanical and estrogen testing.
MSM or placebo treatments: The study will be a randomized double-blinded placebo-controlled trial. MSM or placebo capsules would be provided in a double blinded manner following the second mechanical test. Each individual would consume 2g of either the MSM or placebo control for the remainder of the study.
Intervention Product and Preparation Intervention: MSM (OptiMSM®) is a pure, generally recognized as safe (GRAS) designated product. MSM can be found in small amounts in corn, tomatoes, tea, coffee, milk.
Placebo: Rice flour is a commonly ingested food or additive. Intervention and placebo will be encapsulated in 1g vegetarian capsules (Hypromellose Capsule).
Both intervention and placebo capsules are identically transparent with white powder inside. Capsules containers with 805 capsules (2g per day for each month plus extra) will be prepared, packaged by Bergstrom nutrition and transported with blinded code (A or B) so only individuals responsible for intervention and placebo preparation are removed from conducting the study and are off site (Vancouver, Washington).
Product will be labelled by Bergstrom Nutrition. Subject ID and month (3, 4, or 5) will be filled in manually by University of California, Davis researcher upon randomization.
Determination of knee laxity: Knee laxity will be determined using a GNRB dynamic laximeter following established protocols. Briefly, with the femur held in place, a controlled pressure will be applied to the calf. The pressure increases from 0 to 200 Newtons and a sensor measures kneecap displacement (laxity) in millimeters.
Determination of estrogen levels: Salivary samples will be taken on the first day of menstruation and one day following ovulation for the 4 months of testing (month 1, 2, 4, 5). Estradiol levels in the saliva will be determined using the Estradiol Saliva ELISA kit (Rocky Mountain Diagnostics, CO) as per manufacturer's instructions.
Data Collected:
- Record of menstrual cycle
- Salivary estradiol levels as described above
- Measurements of knee laxity
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double blinded randomized parallel design
| Arm | Type | Receives |
|---|---|---|
| methylsulfonylmethane | Experimental | Dietary Supplement: methylsulfonylmethaneSubjects will be given 2 g/day of methylsulfonylmethane (MSM). Salivary estrogen will be measured around ovulation and menstruation each month for 3 months. Knee laxity will be measures 2 times per month at the same time points (ovulation, menstruation). |
| Placebo | Placebo comparator | Other: PlaceboSubjects will be given 2 g/day placebo (rice flour). Salivary estrogen will be measured around ovulation and menstruation each month for 3 months. Knee laxity will be measures 2 times per month at the same time points as the intervention arm (ovulation, menstruation). |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- • Regular menstrual cycle (~1 x month)
Key exclusion criteria (5 listed)
- • Irregular menstrual cycling (1 x month)
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 |
|---|---|---|
| methylsulfonylmethaneAlso: MSMSubjects will be given 2 g/day methylsulfonylmethane. | Dietary supplement | methylsulfonylmethane |
| PlaceboSubjects will be given 2 g/day placebo (rice flour). | Other | Placebo |
Primary outcome
Kneecap displacement (i.e. knee laxity)
Time frame: 5 months
Knee laxity will be measured at months 4 and 5 after the 3-month intervention period of the study. The measurement will be made in millimeters using a specially designed GNRB arthrometer, which is a computerized and automatic medical device developed and validated by Genourob.
3 secondary outcomes
Weight
Time frame: 1 day
Height
Time frame: 1 day
Body composition
Time frame: 1 day
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 1 Jun 2020.
- Individual participant dataSharing planned: No
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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 methylsulfonylmethane in people with Ligament Injury and Ligament; Laxity, run by University of California, Davis at 1 site in United States.
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 5 inclusion and 5 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 1 Jun 2020. 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 United States. 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?
Kneecap displacement (i.e. knee laxity) (time frame: 5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jun 2020.