Statin Adverse ReactionPhase 4NCT03653663
NIRS to Diagnose SAMS
A Phase 4 study testing Simvastatin 20 mg in people with Statin Adverse Reaction and Skeletal Myopathy, run by Hartford Hospital at 2 sites in United States.
Trial summary
This proposal seeks to determine whether near infrared spectroscopy (NIRS) can differentiate between patients with confirmed SAMS and those with non-specific muscle complaints. NIRS is a non-invasive technique of assessing skeletal muscle tissue oxygenation and mitochondrial function. Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Statin Adverse Reaction, Skeletal Myopathy
- What is being tested?
- Simvastatin 20 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2018to 30 Jul 2020
- Phase
- Phase 4
- 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 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects >40 years of age, equal numbers of age, with a prior history of statin-associated muscle symptoms (SAMS). Subjects will be considered to have had prior statin related complaints and recruited for participation in the study if the following occurred: 1) They developed new pain, cramps, or muscle aching during statin treatment; 2) The symptoms resolved within 4 weeks of stopping the statin; 3) The identical symptoms recurred during repeat statin exposure.
Who cannot join
- Subjects who have had cancer within 5 years of entry, have hepatic disease (ALT > 2 times normal) or renal disease (creatinine > 2 mg/L) since these patients may require more careful monitoring during the study and would be best managed in a totally clinical setting
- Subjects presently treated with other medications known to alter statin metabolism;
- Subjects with hypo- or hyperthyroidism defined as a TSH > 5 or <0.01 IU/L since these conditions are known to be associated with statin intolerance and muscle weakness, respectively;1,2
- Subjects with hepatic dysfunction evidenced by a baseline alanine aminotransferase (ALT) level > 2 UNL;1,2
- Subjects with renal dysfunction defined as a baseline creatinine > 2mg/dl;
- Subjects with physical disabilities prohibiting the handgrip protocol;
Show all 9Show fewer
- Women who are pregnant as determined by a urine pregnancy test using an Accutest Early Pregnancy Test Kit, or who are trying to become pregnant, and/or who have not been using a form of birth control for at least the last 3 months, since the impact of statins on pregnancy-related outcomes has not been well studied;1
- Subjects who regularly use corticosteroids or other drugs known to affect skeletal muscle metabolism or regularly have intramuscular injections that will affect CK levels.
- Subjects who are unwilling to limit their alcohol intake to an average of two or less drinks daily.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hartford Hospital
Hartford, Connecticut, 06102
University of Connecticut
Storrs, Connecticut, 06269-1110
About this study
Official title: Near Infrared Spectroscopy to Diagnose Statin-Associated Muscle Symptoms
This proposal seeks to determine whether near infrared spectroscopy (NIRS) can differentiate between patients with confirmed SAMS and those with non-specific muscle complaints. NIRS is a non-invasive technique of assessing skeletal muscle tissue oxygenation and mitochondrial function. Mitochondrial dysfunction is a possible cause of SAMS, but NIRS has never been evaluated as a diagnostic tool for SAMS. Investigators will enroll 40 patients with a history of SAMS in an 8 wk randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo separated by a 4 wk washout phase. Tissue oxygenation will be measured using NIRS during a short handgrip exercise protocol before and after each treatment period. Investigators will query patients about muscle complaints weekly during both phases of the study with a validated survey to assess muscle pain. Investigators will classify patients as testing positive for SAMS if they report pain on simvastatin and not placebo. Investigators hypothesize that these patients, vs. patients experiencing pain on both treatments, placebo, or neither treatment, will be distinguished by reduced tissue oxygenation during simvastatin treatment relative to placebo, demonstrating efficacy of NIRS as a clinical tool that can be eventually used for the diagnosis and ultimately treatment of SAMS.
Read the detailed description
Study Overview: Forty patients with possible SAMS will be recruited from the Cholesterol Management Center at Hartford Hospital, advertisements and contact with physicians' offices. Subjects will be withdrawn from all statin lipid lowering medications for at least 4 weeks. Subjects will then undergo baseline testing (tissue oxygenation will be measured using NIRS during a short handgrip exercise protocol) and be randomized to treatment with simvastatin 20 mg daily or matching placebo for up to 2 months. Subjects will be called weekly to assess symptoms of muscle pain and administer the Brief Pain Inventory (BPI). NIRS measurements will be repeated and treatment (simvastatin or placebo) will be stopped after 2 months or after subjects have experienced muscle symptoms continuously for one week. After 4 weeks washout, subjects will again be randomized to simvastatin or placebo treatment and the monitoring and measurement processes will be repeated (see study schematic below). Those patients developing muscle symptoms during statin treatment but not during placebo treatment will be considered to have confirmed SAMS. Investigators hypothesize that patients with confirmed SAMS will be distinguished from all other patients with reduced tissue oxygenation during simvastatin treatment relative to placebo, demonstrating efficacy of NIRS as a clinical tool that can be eventually used for the diagnosis and ultimately treatment of SAMS.
Study Subjects: Statin myopathic symptoms have been poorly defined in the medical literature. For the purpose of this study, investigators will use similar criteria as the previous CoQ10 in Statin Myopathy Study when recruiting eligible subjects. Subjects will be considered to have had prior statin related complaints and recruited for participation in the study if the following occurred: 1) They developed new myalgia, cramps, or muscle aching during statin treatment; 2) The symptoms resolved within 4 weeks of stopping the statin; 3) The identical symptoms recurred during repeat statin exposure. Investigators will recruit men and women ≥40 yrs of age, since older age is a risk factor for SAMS and 25% of U.S. adults ≥40 yrs report statin use. Investigators will enroll equal numbers of men and women to improve the generalizability of the results. Investigators will not exclude individuals with diagnosed coronary artery disease, peripheral vascular disease, or an elevated CK off treatment<10 upper normal limit (UNL) because spontaneous elevations in CK levels are normal in the general population. During the study, subjects will be contacted by phone weekly to inquire about muscle complaints using the Brief Pain Inventory (Short Form) (BPI-SF). Results will be recorded on paper forms and entered into the database. After 1 week of persistent symptoms or as soon as possible if the patient has intolerable symptoms, the subject will undergo NIRS testing and be taken off study drug. This reduces undue subject burden such that subjects do not have to maintain statin treatment for multiple weeks with pain symptoms. Subjects who do not report recurrent symptoms will be treated for 8 weeks, at which time they will undergo 4 weeks washout and move on to the crossover phase. Subjects will be reimbursed $200 for study.
- Conditions
- Statin Adverse Reaction, Skeletal Myopathy
- Being tested
- Simvastatin 20 mg, Placebo Oral Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 20 mgDrug
Subjects are treated with 20 mg simvastatin for 8 weeks
Placebo Oral TabletDrug
Subjects are treated with placebo for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 8 weeks treatment with placebo (or until muscle symptoms appear for at least 1 week or are unbearable) Receives: Drug: Placebo Oral Tablet |
| 20 mg simvastatin | Active comparator | 8 weeks treatment with 20 mg simvastatin daily (or until muscle symptoms appear for at least 1 week or are unbearable) Receives: Drug: Simvastatin 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Near infrared spectroscopy
Changes in muscle oxygenation with near infrared spectroscopy during incremental handgrip exercise with drug treatment
Measured: Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable
Secondary outcomes (1)
Creatine kinase
Changes in creatine kinase with drug treatment
Measured: Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2018
- Study start1 Jan 2018
- Primary completion29 Feb 2020 (estimated)
- Study completion30 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Statin Adverse ReactionStudies 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 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, randomized crossover study of placebo vs. 20 mg simvastatin for 8 weeks with a 4 week washout in between
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hartford Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Connecticut
- Responsible party
- Principal investigator, Beth Taylor, Hartford Hospital
- Investigators
- Beth Taylor, PhD, Principal investigator, Hartford Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03653663
- Sponsor's protocol ID
- Grant-In-Aid #17GRNT33661247
- Status last verified
- Feb 2020
- First submitted
- 28 Aug 2018
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mangone LA, Taylor BA, Schmelzer R, Noh SG, White MC, Kwon OS, Thompson PD. Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS). Open Heart. 2024 Feb 22;11(1):e002551. doi: 10.1136/openhrt-2023-002551.
PubMed 38388189
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Near Infrared Spectroscopy to Diagnose Statin-Associated Muscle Symptoms
- ClinicalTrials.gov ID
- NCT03653663
- Acronym / sponsor ID
- Grant-In-Aid #17GRNT33661247
- Conditions
- Statin Adverse Reaction, Skeletal Myopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hartford HospitalUniversity, hospital or other
- Collaborators
- University of Connecticut
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 29 Feb 2020 (estimated)
- Study completion
- 30 Jul 2020 (estimated)
- First posted
- 31 Aug 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.
This proposal seeks to determine whether near infrared spectroscopy (NIRS) can differentiate between patients with confirmed SAMS and those with non-specific muscle complaints. NIRS is a non-invasive technique of assessing skeletal muscle tissue oxygenation and mitochondrial function. Mitochondrial dysfunction is a possible cause of SAMS, but NIRS has never been evaluated as a diagnostic tool for SAMS. Investigators will enroll 40 patients with a history of SAMS in an 8 wk randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo separated by a 4 wk washout phase. Tissue oxygenation will be measured using NIRS during a short handgrip exercise protocol before and after each treatment period. Investigators will query patients about muscle complaints weekly during both phases of the study with a validated survey to assess muscle pain. Investigators will classify patients as testing positive for SAMS if they report pain on simvastatin and not placebo. Investigators hypothesize that these patients, vs. patients experiencing pain on both treatments, placebo, or neither treatment, will be distinguished by reduced tissue oxygenation during simvastatin treatment relative to placebo, demonstrating efficacy of NIRS as a clinical tool that can be eventually used for the diagnosis and ultimately treatment of SAMS.
Detailed description
Study Overview: Forty patients with possible SAMS will be recruited from the Cholesterol Management Center at Hartford Hospital, advertisements and contact with physicians' offices. Subjects will be withdrawn from all statin lipid lowering medications for at least 4 weeks. Subjects will then undergo baseline testing (tissue oxygenation will be measured using NIRS during a short handgrip exercise protocol) and be randomized to treatment with simvastatin 20 mg daily or matching placebo for up to 2 months. Subjects will be called weekly to assess symptoms of muscle pain and administer the Brief Pain Inventory (BPI). NIRS measurements will be repeated and treatment (simvastatin or placebo) will be stopped after 2 months or after subjects have experienced muscle symptoms continuously for one week. After 4 weeks washout, subjects will again be randomized to simvastatin or placebo treatment and the monitoring and measurement processes will be repeated (see study schematic below). Those patients developing muscle symptoms during statin treatment but not during placebo treatment will be considered to have confirmed SAMS. Investigators hypothesize that patients with confirmed SAMS will be distinguished from all other patients with reduced tissue oxygenation during simvastatin treatment relative to placebo, demonstrating efficacy of NIRS as a clinical tool that can be eventually used for the diagnosis and ultimately treatment of SAMS.
Study Subjects: Statin myopathic symptoms have been poorly defined in the medical literature. For the purpose of this study, investigators will use similar criteria as the previous CoQ10 in Statin Myopathy Study when recruiting eligible subjects. Subjects will be considered to have had prior statin related complaints and recruited for participation in the study if the following occurred: 1) They developed new myalgia, cramps, or muscle aching during statin treatment; 2) The symptoms resolved within 4 weeks of stopping the statin; 3) The identical symptoms recurred during repeat statin exposure. Investigators will recruit men and women ≥40 yrs of age, since older age is a risk factor for SAMS and 25% of U.S. adults ≥40 yrs report statin use. Investigators will enroll equal numbers of men and women to improve the generalizability of the results. Investigators will not exclude individuals with diagnosed coronary artery disease, peripheral vascular disease, or an elevated CK off treatment<10 upper normal limit (UNL) because spontaneous elevations in CK levels are normal in the general population. During the study, subjects will be contacted by phone weekly to inquire about muscle complaints using the Brief Pain Inventory (Short Form) (BPI-SF). Results will be recorded on paper forms and entered into the database. After 1 week of persistent symptoms or as soon as possible if the patient has intolerable symptoms, the subject will undergo NIRS testing and be taken off study drug. This reduces undue subject burden such that subjects do not have to maintain statin treatment for multiple weeks with pain symptoms. Subjects who do not report recurrent symptoms will be treated for 8 weeks, at which time they will undergo 4 weeks washout and move on to the crossover phase. Subjects will be reimbursed $200 for study.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, randomized crossover study of placebo vs. 20 mg simvastatin for 8 weeks with a 4 week washout in between
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo Oral Tablet8 weeks treatment with placebo (or until muscle symptoms appear for at least 1 week or are unbearable) |
| 20 mg simvastatin | Active comparator | Drug: Simvastatin 20 mg8 weeks treatment with 20 mg simvastatin daily (or until muscle symptoms appear for at least 1 week or are unbearable) |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Subjects >40 years of age, equal numbers of age, with a prior history of statin-associated muscle symptoms (SAMS). Subjects will be considered to have had prior statin related complaints and recruited for participation in the study if the following occurred: 1) They developed new pain, cramps, or muscle aching during statin treatment; 2) The symptoms resolved within 4 weeks of stopping the statin; 3) The identical symptoms recurred during repeat statin exposure.
Key exclusion criteria (9 listed)
- Subjects who have had cancer within 5 years of entry, have hepatic disease (ALT > 2 times normal) or renal disease (creatinine > 2 mg/L) since these patients may require more careful monitoring during the study and would be best managed in a totally clinical setting
- Subjects presently treated with other medications known to alter statin metabolism;
- Subjects with hypo- or hyperthyroidism defined as a TSH > 5 or <0.01 IU/L since these conditions are known to be associated with statin intolerance and muscle weakness, respectively;1,2
- Subjects with hepatic dysfunction evidenced by a baseline alanine aminotransferase (ALT) level > 2 UNL;1,2
- Subjects with renal dysfunction defined as a baseline creatinine > 2mg/dl;
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 |
|---|---|---|
| Simvastatin 20 mgSubjects are treated with 20 mg simvastatin for 8 weeks | Drug | 20 mg simvastatin |
| Placebo Oral TabletSubjects are treated with placebo for 8 weeks | Drug | Placebo |
Primary outcome
Near infrared spectroscopy
Time frame: Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable
Changes in muscle oxygenation with near infrared spectroscopy during incremental handgrip exercise with drug treatment
1 secondary outcome
Creatine kinase
Time frame: Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Derived from this study: PubMed 38388189Mangone LA, Taylor BA, Schmelzer R, Noh SG, White MC, Kwon OS, Thompson PD. Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS). Open Heart. 2024 Feb 22;11(1):e002551. doi: 10.1136/openhrt-2023-002551.
- 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.
Beth Taylor, PhD principal investigator
Hartford Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin 20 mg in people with Statin Adverse Reaction and Skeletal Myopathy, run by Hartford Hospital at 2 sites 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 1 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Near infrared spectroscopy (time frame: Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable). 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 NCT03653663, which also lists 1 linked publication.
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 13 Feb 2020.