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NIRS to Diagnose SAMS

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ClinicalTrials.gov Identifier: NCT03653663
Recruitment Status : Active, not recruiting
First Posted : August 31, 2018
Last Update Posted : February 13, 2020
Sponsor:
Collaborator:
University of Connecticut
Information provided by (Responsible Party):
Beth Taylor, Hartford Hospital

Tracking Information
First Submitted Date  ICMJE August 28, 2018
First Posted Date  ICMJE August 31, 2018
Last Update Posted Date February 13, 2020
Actual Study Start Date  ICMJE January 1, 2018
Estimated Primary Completion Date February 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
Creatine kinase [ Time Frame: Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable ]
Changes in creatine kinase with drug treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NIRS to Diagnose SAMS
Official Title  ICMJE Near Infrared Spectroscopy to Diagnose Statin-Associated Muscle Symptoms
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
All members of the investigative team as well as the patients are blinded to treatment until all subjects have completed the study.
Primary Purpose: Diagnostic
Condition  ICMJE
  • Statin Adverse Reaction
  • Skeletal Myopathy
Intervention  ICMJE
  • Drug: Simvastatin 20 mg
    Subjects are treated with 20 mg simvastatin for 8 weeks
  • Drug: Placebo Oral Tablet
    Subjects are treated with placebo for 8 weeks
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    8 weeks treatment with placebo (or until muscle symptoms appear for at least 1 week or are unbearable)
    Intervention: Drug: Placebo Oral Tablet
  • Active Comparator: 20 mg simvastatin
    8 weeks treatment with 20 mg simvastatin daily (or until muscle symptoms appear for at least 1 week or are unbearable)
    Intervention: Drug: Simvastatin 20 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 29, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2020
Estimated Primary Completion Date February 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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;
  • 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03653663
Other Study ID Numbers  ICMJE Grant-In-Aid #17GRNT33661247
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Beth Taylor, Hartford Hospital
Study Sponsor  ICMJE Hartford Hospital
Collaborators  ICMJE University of Connecticut
Investigators  ICMJE
Principal Investigator: Beth Taylor, PhD Hartford Hospital
PRS Account Hartford Hospital
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP