Genetically Guided Statin Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Duke University
Sponsor:
Collaborator:
David Grant U.S. Air Force Medical Center
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01894230
First received: July 3, 2013
Last updated: May 1, 2014
Last verified: May 2014

July 3, 2013
May 1, 2014
July 2013
November 2015   (final data collection date for primary outcome measure)
Change in Medication adherence [ Time Frame: Baseline, three and eight months ] [ Designated as safety issue: No ]
The primary outcome of this study is the Morisky Medication Adherence Survey (MMAS), a self-reported measure of adherence, collected at baseline and at 3 and 8 months of follow-up. The eight-item MMAS survey will be used. This is a modified version of the original four-item MMAS capturing further aspects of adherence behavior. The survey includes 8 yes/no items that are summed to create an overall adherence score ranging from of 0 to 8, with higher scores indicating better adherence. The primary hypothesis is that the genetically guided statin therapy leads to greater adherence of statin therapy, corresponding to a higher MMAS score.
Same as current
Complete list of historical versions of study NCT01894230 on ClinicalTrials.gov Archive Site
  • Change in Low density lipoprotein cholesterol (LDLc) [ Time Frame: Baseline, three and eight months ] [ Designated as safety issue: No ]
    The continuous outcomes LDLc will be modeled as a linear regression with arm, genotype, and site as predictors. Baseline LDLc will also be included as a covariate to account for baseline variability
  • Medication possession ratio (MPR) [ Time Frame: Eight months ] [ Designated as safety issue: No ]

    Medication possession ration will be calculated based on number of statin medication refills over time from randomization to end of follow up.

    MPR is calculated as follows:

    1. Sum of the days' supply of all statin medications is the sum of the number of pills dispensed for each statin prescription during follow up (taken from 3-month, 4-month and 8-month statin utilization review)
    2. Sum of the days of follow up = date of 8-month follow up survey - date of randomization
    3. MPR = #1/#2 MPR will be modeled as a linear regression with arm, genotype, and site as predictors.
  • New statin prescriptions [ Time Frame: Three months ] [ Designated as safety issue: No ]
    The number of new prescriptions is binary and will be modeled with logistic regression with arm, genotype, and site as predictors. Any variables imbalanced between arms will also be included as covariates.
  • Change in Brief Pain Inventory (BPI) [ Time Frame: Three and eight months ] [ Designated as safety issue: No ]

    Brief Pain Inventory data will be taken from 3 and 8-month follow up Patient Surveys.

    • Pain severity and pain interference will be compared between groups
    • Both of these measures will be modeled as a linear regression with arm, genotype, and site as predictors. Transformations of the response may be explored depending on the distribution of the regression residuals.
    • Baseline pain scores will also be included as a covariate to account for baseline variability.
  • Change in SF-12 Health Survey [ Time Frame: Three and eight month follow up ] [ Designated as safety issue: No ]
    • 3 month and 8-month SF12 scores will be compared
    • Both of these measures will be modeled as a linear regression with arm, genotype, and site as predictors. Transformations of the response may be explored depending on the distribution of the regression residuals.
    • Baseline SF-12 scores will also be included as a covariate to account for baseline variability.
  • Physical activity [ Time Frame: Eight months ] [ Designated as safety issue: No ]
    • Activity levels will be compared at the end of 8-months
    • Activity levels are defined by a three-level ordinal variable. A proportional odds model will be used with arm, genotype, and site as predictors. The assumption of proportional odds will be checked, and if it is not met, a multinomial regression model will be used.
    • Baseline physical activity will also be included as a covariate to account for baseline variability.
  • Change in Beliefs about medications (BMQ) [ Time Frame: Baseline, three and eight months ] [ Designated as safety issue: No ]
    • Questionnaire administered at baseline, 3 months, and 8 months
    • This instrument assesses beliefs regarding necessity and concerns related to disease-specific medications
    • The score ranges from 5 to 25 representing the sum of 5 questions. The score represents a count and will be modeled with Poisson regression with arm, site, and genotype as predictors.
    • Baseline BMQ scores will also be included as a covariate to account for baseline variability.
Same as current
Not Provided
Not Provided
 
Genetically Guided Statin Therapy
Genetically Guided Statin Therapy to Improve Medication Adherence

The purpose of this study is to examine if using genetics can improve statin adherence in patients who should be taking statins but are not because of prior side effects. This study will assist physicians/providers in making a personalized health care plan for prevention of cardiovascular disease.

HMG Co-A reductase inhibitors ("statins") are commonly prescribed to lower low density lipoprotein cholesterol (LDLc) and to prevent cardiovascular disease (CVD), a leading cause of morbidity and mortality. Long-term adherence to statins in the primary care environment is challenging; consequences of statin non-adherence include higher LDLc levels, hospitalizations, costs, and death due to CVD.

Medication non-adherence is complex and multifactorial and can be associated with a number of factors including medication cost, complexity of medication regimen, poor provider-patient relationship / communication, and adverse side effects. For statins, side effects such as muscle aches, cramping, and pain (referred to broadly as statin-related myopathy) are a frequent cause of non-adherence. These symptoms are non-specific and are frequent reasons for stopping statin therapy, due to patient or provider concern about the possibility of statin-related myopathy. Many patients may be needlessly deprived of the cardiovascular benefits of long-term statin use.

A genetic risk factor for statin myopathy and subsequent non-adherence has recently been identified. In a genome-wide association study, a genetic variant (named SLCO1B1*5) was a main contributor of statin myopathy. It was demonstrated that the SLCO1B1*5 variant is not only a predictor of myopathy, but also of premature statin discontinuation. The risk with the *5 allele is statin specific: greatest with simvastatin and atorvastatin use, the least with pravastatin or rosuvastatin. Therefore, the SLCO1B1*5 variant is common, can predict myopathy, subsequent non-adherence, and due to its statin-specific effects creates a novel research paradigm for personalizing statins to an individual's genetic profile. Carriers of the SLCO1B1*5 variant may do best on rosuvastatin, pravastatin, or fluvastatin whereas non-carriers may be treated with any statin.

The objective of this study is to conduct a randomized trial comparing two strategies:

  1. genetically guided statin therapy vs.
  2. usual care (i.e., a strategy without genetics) on the effects of statin adherence and LDLc lowering.

The overall hypothesis is that genetically guided statin therapy will lead to greater statin adherence and lower LDLc when compared to a non-guided strategy. The design of this trial will randomize primary care patients within Duke University Health System (DUHS) and travis Air Force Base (TAFB) clinics that are nonadherent to statins due to prior side-effects in an unblinded, 1:1 fashion, stratified by SLCO1B1*5 genotype.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Hypercholesterolemia
  • HMG COA Reductase Inhibitor Adverse Reaction
  • Genetic: Reporting for SLCO1B1*5 allele at randomization
    Reporting of genetic test results to patient and provider at randomization
  • Genetic: Reporting for SLCO1B1*5 allele at the end
    Usual care recommendations provided to patient and provider at randomization. Genotyping results provided at the end of study.
  • Genetic: Genetic testing for SLCO1B1*5 allele
    Blood test for SLCO1B1*5 allele
  • Experimental: Genotype results plus usual care
    • Genetic testing for SLCO1B1*5 allele
    • Reporting for SLCO1B1*5 allele at randomization
    Interventions:
    • Genetic: Reporting for SLCO1B1*5 allele at randomization
    • Genetic: Genetic testing for SLCO1B1*5 allele
  • Active Comparator: Usual care only
    • Genetic testing for SLCO1B1*5 allele
    • Reporting for SLCO1B1*5 allele at the end of study
    Interventions:
    • Genetic: Reporting for SLCO1B1*5 allele at the end
    • Genetic: Genetic testing for SLCO1B1*5 allele
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
375
January 2016
November 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Current patient (defined as seen in the last year) of the Duke Primary Care at Pickett Road, Pickens Family Medicine Center or Travis AFB
  • Age greater than or equal to 18 years
  • Current non-utilization of statin therapy for either of the following reasons: (a) Prior side effects thought to be attributed by the patient to statin use AND/OR (b) Physician removal of statin due to presumed associated side effects
  • No statin use for the past 6 weeks
  • Active email account
  • Computer access available in order to complete on-line surveys
  • Ability to provide informed consent

Exclusion Criteria:

  • Prior rhabdomyolysis, or CK elevation > 10 times the upper limit of normal with any statin therapy
  • Prior unexplained elevation in hepatic enzymes (AST or ALT > 3 times upper limit of normal) with any statin therapy
  • Current daily grapefruit juice usage (on average >1quart/day)
  • Expected long term use (longer than 3 months) of the following medications known to interfere with statin metabolism or disposition at time of enrollment until the randomization is complete. However, short-term (<14 days) is allowed for the duration of the study
  • Participation in a drug research study in the past 30 days
  • Previous use of 4 or more statins
Both
18 Years and older
No
United States
 
NCT01894230
Pro00044989, Pro00045542
No
Duke University
Duke University
David Grant U.S. Air Force Medical Center
Principal Investigator: Deepak Voora, MD Duke University
Principal Investigator: Nicholas Milazzo, BS Pharm, MBA David Grant US Air Force Medical Center
Duke University
May 2014

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