Metabolic Syndrome, Stable Angina
Conditions
Keywords
Stable Angina, Metabolic Syndrome, Women, Biomarkers
Brief summary
The purpose of this study is to determine the effects of ranolazine on different markers of cardiometabolic disease in women with stable angina.
Detailed description
Evaluate the ability of ranolazine to favorably modify thrombogenic, inflammatory, lipogenic, oxidative stress and hormonal biomarkers in a relatively short period of time in a group of ethnically diverse women with chronic stable angina and metabolic syndrome.
Interventions
DRUGRanolazine
Ranolazine 500 mg from baseline to week 3 and 1000 mg thereafter until week 24
OTHERPlacebo
Matching placebo tablets daily for 24 weeks.
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with chronic stable angina (\> 3 months) on evidence based adequate therapy * Evidence of stable coronary artery disease by any of these: * MI, PCI or CABG \> 30 days prior to enrollment or * Angiography showing \> 50% stenosis in major vessel, branch or bypass graft \> 30 days of enrollment or * Abnormal stress MPI nuclear study, or DBA stress echo where the decision has been to treat medically and where angina has remained stable for \>= 3 months * Evidence of the Metabolic Syndrome: As defined by ATP III criteria i.e 3/5 of following Abdominal circumference F \> 88 cm (35 in), M \> 102 cm (40 in) Hypertriglyceridemia ≥ 150 mg/dl HDL F \< 50 mg/dl M \< 40 mg/dl Blood Pressure ≥130/85 Fasting Glucose ≥100 mg/dl For reproductive age women, a negative urine pregnancy test is required if all other inclusion criteria are met.
Exclusion criteria
* Exclusion of patients with contraindications to use of RANEXA, including patients on CYP3A4 inducers/potent inhibitors, and patients with liver cirrhosis. * Exclusion of Patients with CrCl \< 30 mL/min * Limit dose of RANEXA to 500mg BID in patients on concurrent diltiazem/ verapamil * Limit concurrent simvastatin to 20 mg/day * Limit concurrent metformin to 1700 mg/day Additional Exclusion * Patients with variable -inconsistent symptoms * Patients with unstable coronary artery disease or revascularization within 30 days of enrollment. * Patients who have known severe liver disease. * Patients already receiving maximal ranolazine therapy for more than 4 weeks * Presence of diabetes (AIC≥ 6.5 and /or on insulin therapy or anti-diabetic medication other than metformin) unstable hypothyroidism, active infection, active cancer (or ongoing chemotherapy and/or radiation within a year who are not on remission) and/or recent major surgery or illness. * Patients with any contraindication to ranolazine see above * Women of reproductive age are excluded if they are planning to become pregnant in the next 6 -12 months after randomization. * Patients who are pregnant or lactating * Documented allergic reaction to ranolazine in the past. * Unexplained prolongation of the QTc \> 500 milliseconds. * Current or planned co-administration of moderate CYP3A inhibitors (eg, diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products) is not a full contraindication, if meet inclusion criteria otherwise, these patients could be accepted in trial but dose will be limited to 500 mg BID as stated previously. * Current or planned co-administration of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir) OR strong CYP3A inducers (eg, rifampin, rifabutin, rifapentine, phenobarbital, phenytoin,carbamazepine, and St. John's Wort) is a contraindication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Ranolazine on Hemoglobin A1C | Change from baseline to 24 weeks | Will evaluate the impact of ranolazine in HgbA1C in women with Metabolic Syndrome (MBS) |
| Impact of Ranolazine on HDL-C Levels in Subjects | Change from Baseline to 24 weeks | Will evaluate the impact of ranolazine in HDL-C levels in women with metabolic syndrome |
Countries
United States
Participant flow
Recruitment details
Recruitment period: 7/21/14 - 7/2/18 Location: UF Jacksonville Outpatient Cardiology clinic
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Ranolazine would start with 500 mg BID and be force titrated to 1 gram po BID after 3 weeks. Down titration would only be allowed for side effects. This would be on top of all standard medical therapy.
Ranolazine: Ranolazine 500 mg from baseline to week 3
Ranolazine: Ranolazine 1000mg daily at week 3 until weeks 24. | 16 |
| Placebo Placebo arm would start with 500 mg matching placebo tablet BID and be force titrated to 1 gram matching placebo tablet twice a day after 3 weeks. Down titration would only be allowed for side effects (if reported). This would be on top of all standard medical therapy.
Placebo: Matching placebo tablets daily for 24 weeks. | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Starting Dose Ranolazine 500 mg BID | Adverse Event | 1 | 0 |
| Starting Dose Ranolazine 500 mg BID | Lost to Follow-up | 2 | 3 |
| Starting Dose Ranolazine 500 mg BID | Withdrawal by Subject | 1 | 0 |
| Titrated to Ranolazine 1000mg BID | Adverse Event | 2 | 0 |
| Titrated to Ranolazine 1000mg BID | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Ranolazine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 12 Participants | 26 Participants |
| Region of Enrollment United States | 16 participants | 17 participants | 33 participants |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 33 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 3 / 16 | 0 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 |
Outcome results
Primary
Impact of Ranolazine on HDL-C Levels in Subjects
Will evaluate the impact of ranolazine in HDL-C levels in women with metabolic syndrome
Time frame: Change from Baseline to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine Treated | Impact of Ranolazine on HDL-C Levels in Subjects | 6.6 percentage of change in HDL | Standard Deviation 15.7 |
| Placebo | Impact of Ranolazine on HDL-C Levels in Subjects | 6.5 percentage of change in HDL | Standard Deviation 46.6 |
Primary
Impact of Ranolazine on Hemoglobin A1C
Will evaluate the impact of ranolazine in HgbA1C in women with Metabolic Syndrome (MBS)
Time frame: Change from baseline to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine Treated | Impact of Ranolazine on Hemoglobin A1C | -5 percent change | Standard Deviation 6.2 |
| Placebo | Impact of Ranolazine on Hemoglobin A1C | 2.6 percent change | Standard Deviation 9.1 |