NIRS to Diagnose SAMS

NCT03653663 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: Grant-In-Aid #17GRNT33661247
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Statin Adverse Reaction; Skeletal Myopathy

Outcome Measures

Primary Outcomes (1)

• Near infrared spectroscopy

  Changes in muscle oxygenation with near infrared spectroscopy during incremental handgrip exercise with drug treatment

  Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable

Secondary Outcomes (1)

• Creatine kinase

  Up to 8 weeks of treatment, or until muscle symptoms have occurred for 1 week or are intolerable

Study Arms (2)

Placebo

PLACEBO COMPARATOR

8 weeks treatment with placebo (or until muscle symptoms appear for at least 1 week or are unbearable)

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)

Drug: Simvastatin 20 mg

Interventions

Simvastatin 20 mg DRUG

Subjects are treated with 20 mg simvastatin for 8 weeks

20 mg simvastatin

Placebo Oral Tablet DRUG

Subjects are treated with placebo for 8 weeks

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hartford Hospital: lead
• University of Connecticut: collaborator

Study Sites (2)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

University of Connecticut

Storrs, Connecticut, 06269-1110, United States

Location

Related Publications (1)

• 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.

  PMID: 38388189 DERIVED

MeSH Terms

Interventions

Simvastatin

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Beth Taylor, PhD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All members of the investigative team as well as the patients are blinded to treatment until all subjects have completed the study.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Exercise Physiology Research

Model Details: Double-blind, randomized crossover study of placebo vs. 20 mg simvastatin for 8 weeks with a 4 week washout in between

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: August 31, 2018
• Study Start: January 1, 2018
• Primary Completion: February 29, 2020
• Study Completion: July 30, 2020
• Last Updated: February 13, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)