Quality of Life in Patients With Statin-Associated Myopathy

• Sponsor: Rockefeller University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00850460
• Collaborator: Cornell University (Other), Adelphi University (Other)
• Enrollment: 14
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The proposed study will focus on possible effects of statins on muscle strength and why they become tired more easily, quality of life, and measurements to understand why muscles are not able to fully utilize fats. The investigators are specifically interested in statin users and the impact of muscle symptoms on daily activities and quality of life.

This study hypothesize that patients with likely statin-associated myopathy have a metabolic dysregulation in fuel utilization such that compared to patients continuing statins, those on placebo will show:

1. improved Individualized Neuromuscular Quality of Life (INQoL) and Short Form-36 (SF-36) scores (primary end point)

2. alleviation of muscle symptoms,

3. increased utilization of fatty acids as a fuel source reflected by the metabolic test results

4. decreased intramyocellular lipid (IMCL)

5. improved insulin sensitivity.

Condition or Disease	Intervention/Treatment	Phase
Statin Adverse Reaction	Drug: Statins; Drug: Placebo	Phase 4

Detailed Description

The proposed study will focus on possible effects of statins on muscle strength and quality of life, and measurements to understand why muscles of statin users are not able to fully utilize fats. The investigators are specifically interested in statin users and the impact of muscle symptoms on daily activities and quality of life.

This study hypothesizes that patients with likely statin-associated myopathy have a metabolic dysregulation in fuel utilization such that compared to patients continuing statins, those on placebo will show:

1. improved INQoL and SF-36 scores (primary end point)

2. alleviation of muscle symptoms,

3. increased utilization of fatty acids as a fuel source reflected by the metabolic test results

4. decreased IMCL

5. improved insulin sensitivity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Official Title: Quality of Life and Metabolic Alterations in Patients With Statin-Associated Myopathy
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Lactose placebo pill	Drug: Placebo; Placebo pills will consist of lactose and will be given one capsule once daily; Other Names: lactose pills
Active Comparator: Statins Statin medications	Drug: Statins; Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.; Other Names: atorvastatin, simvastatin, pravastatin, rosuvastatin

Outcome Measures

Primary Outcome Measures

1. Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8 [Week 0 to Week 8]

   Scores from the self-administered INQoL questionnaire will be compared at the start of the study (Week 0) and at the end (Week 8) between the statin-treated group and the placebo group. Scores range from 0-100, with 100 being a better outcome. Measures reported are the means of Week 0 and week 8, measures of dispersion is the range of the results (3 per group).

2. Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8 [Week 0 to Week 8]

   Scores from the self-administered SF-36 (Physical component) questionnaire were measured at the start (Week 0) of the study and at the end (Week 8) among patients in the placebo- and statin-treated group. Mean scores range from 0 (minimum) - 100 (maximum) with higher mean scores reflecting better outcomes. Measures reported are the means of Week 0 and week 8, measures of dispersion is the range of scores.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• males and females 30-60 yrs old

• experiencing muscle pain, weakness, numbness or cramping that they perceive to interfere with activities of daily living (ADLs), but able to ambulate independently (in order to perform exercise tests)

• muscle symptoms started/ occurred within one year of starting statin treatment or within one year of changing statin brand or dose adjustment

• currently taking a statin (has been taking medications ≥ 80% of the time or at least 5 days/week)

• ≤ 15% probability of having a cardiovascular (CV) event in the next 10 years calculated using an online CV risk calculator (while on current statin) for the questionnaire portion; AND with a low or a moderate American College of Sports Medicine (ACSM) risk stratification for a cardiovascular event during a treadmill test for the full metabolic study

• must agree to have a letter sent to inform the health care provider who prescribed the statin of study participation except for subjects referred by Metropolitan Hospital physicians

Exclusion Criteria:

• concomitant treatment with other lipid-lowering agents

• impaired liver or kidney function ( alanine aminotransferase (ALT) or asparate aminotransferase (AST) ≥ 3x upper limit of normal, creatinine ≥ 3x or creatine phosphokinase (CPK) ≥ 5x upper limit of normal)

• untreated hypo or hyperthyroidism

• current treatment with other medications known to increase risk of myopathy (e.g. cyclosporine, azithromycin, erythromycin and other macrolide antibiotics, azole antifungals, fusidic acid, digoxin)

• documented history of muscle disorder or myopathy other than statin-associated myopathy

• anemia (Hb< 110 g/dL)

• cancer within 5 years of enrollment except basal or squamous cell carcinoma (CA) of the skin

• diabetes

• HIV-1 infection

• Uncontrolled blood pressure ≥ 160/100

• known coronary artery disease or peripheral vascular disease

• chronic illnesses such as lupus, rheumatoid arthritis, psoriasis

• any condition, that at the investigators' discretion would impact/ bias the study data

• long term oral, nasal, or inhaler steroid use > 6 months

• on Hormone Therapy except for thyroid replacement

• alcohol consumption ≥ 40 g/day (3 glasses/day wine or beers or binge drinking ≥ 4 glasses/night)

• engaged in significant amounts of sport or strenuous leisure activity (> 60 min four times per week)

• surgery in the past 6 months except for minor excision/incision procedures,

• 12-L electrocardiogram demonstrating old/new myocardial infarction/ ischemia or other findings that, at the cardiologist's discretion, may put the subject at high risk

• cognitive impairment that prevents comprehension of questionnaires

• inability to read English (questionnaire language)

Exclusions for the metabolic study:

• currently taking beta blockers

• body mass index > 28 kg/m2

• premenopausal females < 50 yrs (menopause defined as 12 consecutive months without menstruation (in order to avoid the confounding effect of the menstrual cycle phase on fuel selection)

• physical disability or previous injury that prevents safe exercise testing

• do not meet the magnetic resonance spectroscopy (MRS) prescreening criteria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rockefeller University	New York	New York	United States	10065

Sponsors and Collaborators

• Rockefeller University
• Cornell University
• Adelphi University

Investigators

• Principal Investigator: Patricia D Maningat, MD, Rockefeller University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rockefeller University
• ClinicalTrials.gov Identifier: NCT00850460
• Other Study ID Numbers: PAM-0655
• First Posted: Feb 25, 2009
• Last Update Posted: Nov 6, 2016
• Last Verified: Sep 1, 2016

• Additional relevant MeSH terms: Atorvastatin; Rosuvastatin Calcium; Simvastatin; Pravastatin

Study Results

Participant Flow

Recruitment Details	Advertisements were placed (internet, radio, print) and a screening phone questionnaire was administered by study staff to determine potential inclusion. A collaboration with the Metropolitan Hospital (NY) was also established for potential referrals.
Pre-assignment Detail	Subjects in whom statins are possibly causative, using the World Health Organization (WHO)-Causality Assessment form, were invited to the outpatient clinic for 2 screening visits. Subjects found to be at high risk for cardiovascular events and those unwilling to be shifted to placebo were not enrolled.

Arm/Group Title	Placebo	Statins
Arm/Group Description	Lactose placebo pill Placebo: Placebo pills will consist of lactose and will be given one capsule once daily	Statin medications Statins: Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.
Period Title: Overall Study
STARTED	7	7
Started - Week 0	7	7
Completion - Week 8	3	3
COMPLETED	3	3
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Placebo	Statins	Total
Arm/Group Description	Lactose placebo pill Placebo: Placebo pills will consist of lactose and will be given one capsule once daily	Statin medications Statins: Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.	Total of all reporting groups
Overall Participants	3	3	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	3 100%	6 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	1 16.7%
Male	3 100%	2 66.7%	5 83.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 33.3%	0 0%	1 16.7%
White	1 33.3%	2 66.7%	3 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 33.3%	1 33.3%	2 33.3%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Individualized Neuromuscular Quality of Life (INQoL) Mean Scores From Week 0 to Week 8
Description	Scores from the self-administered INQoL questionnaire will be compared at the start of the study (Week 0) and at the end (Week 8) between the statin-treated group and the placebo group. Scores range from 0-100, with 100 being a better outcome. Measures reported are the means of Week 0 and week 8, measures of dispersion is the range of the results (3 per group).
Time Frame	Week 0 to Week 8

Outcome Measure Data

Analysis Population Description

Three patients from each group completed the questionnaire portion of the study at Week 0 and Week 8.

Arm/Group Title	Placebo	Statins
Arm/Group Description	Lactose placebo pill Placebo: Placebo pills will consist of lactose and will be given one capsule once daily	Statin medications Statins: Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.
Measure Participants	3	3
Week 0 Mean Score	65	76
Week 8 Mean Score	67	50

2. Primary Outcome

Title	Individualized Short Form-36 (SF-36) Mean Scores (Physical Component) From Week 0 to Week 8
Description	Scores from the self-administered SF-36 (Physical component) questionnaire were measured at the start (Week 0) of the study and at the end (Week 8) among patients in the placebo- and statin-treated group. Mean scores range from 0 (minimum) - 100 (maximum) with higher mean scores reflecting better outcomes. Measures reported are the means of Week 0 and week 8, measures of dispersion is the range of scores.
Time Frame	Week 0 to Week 8

Outcome Measure Data

Analysis Population Description

Three patients from each group completed the questionnaire portion of the study at Week 0 and Week 8.

Arm/Group Title	Placebo	Statins
Arm/Group Description	Lactose placebo pill Placebo: Placebo pills will consist of lactose and will be given one capsule once daily	Statin medications Statins: Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.
Measure Participants	3	3
Week 0 Mean Score	50	53
Week 8 Mean Score	56	48

Adverse Events

Time Frame	Adverse event data were collected from the time the subjects were enrolled in the study until study termination (eight weeks). The study ran for two years.
Arm/Group Title	Placebo		Statins
Arm/Group Description	Lactose placebo pill Placebo: Placebo pills will consist of lactose and will be given one capsule once daily		Statin medications Statins: Subjects will be randomized to continue their statin dosage or placebo for 8 weeks. They will stay on the same dosage as prescribed by their physician. Usual dosage for atorvastatin 10-80 mg/tab once daily by mouth; simvastatin 20-80 mg/tab once daily by mouth; pravastatin 10-80 mg/tab once daily by mouth; rosuvastatin 5-20 mg/tab once daily by mouth.
All Cause Mortality
	Placebo		Statins
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Statins
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Statins
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.