Effect of Pharmacological Reversal of Hyperuricemia on Features of the Metabolic Syndrome

Study ID
STU 052011-103

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
De'Anica Gonzalez
214-648-6790
deanica.gonzalez@utsouthwestern.edu

Principal Investigator
Naim Maalouf

Summary

Prospective, observational study, with measures of insulin sensitivity, fractional excretion of uric acid, blood pressure and lipid profile are measured prior to and 6 months after treatment with febuxostat.

The population to be enrolled will be 30 subjects with gout, hence it is somewhat homogeneous. in nHaneS iii, the prevalence of metabolic syndrome according to the revised nCeP/aTP iii criteria was 62.8% among individuals with gout and 83.3%among individuals who had gout and were exposed to allopurinol or uricosuric agents. Therefore, the vast majority of subjects likely to be included in our study will have the metabolic syndrome. While the subjects will be homogeneous with respect to the presence of gout, there will be heterogeneity in terms of therapy for co-morbidities, but all co-morbidities will be controlled at study entry (based on inclusion/exclusion criteria). This heterogeneity is expected, and we will test whether febuxostat alters HoMa-iR and other secondary endpoints irrespective of baseline severity of diabetes, hypertension, dyslipidemia.

To avoid the potential effect of drug treatment, we plan to recruit subjects whose diabetes and hypertension are relatively well controlled based on Hba1c ([LessThanorequalTo] 7.0%) and blood pressure measurement ([Less Than]160/90 mmHg in the past 6 months) at study entry. if additional issues/abnormalities arise during study follow-up, subjects will be asked to contact their primary care physician to address these. Medication changes will be tracked at each follow-up visit. at the time of analysis, subjects who had their blood pressure medications (dose, type) changed during the 6 months of study will be excluded from the analysis of blood pressure changes vs. febuxostat therapy. Similarly, subjects who had their diabetes medications changed during the 6 months of therapy will be excluded from the analysis of HoMa-iR changes vs. febuxostat therapy.

Study Protocol:
Potential study subjects will be identified by their treating physicians, who will refer them for participation in this study. at that point, if the subject is interested, he/she will be provided with a phone number to contact the study coordinator. alternatively, if the subject is agreeable, the treating physician will provide the patient's contact information to the study coordinator. They will be screened initially through a telephone interview and review of available laboratory results for inclusion and exclusion criteria. Subjects may have blood drawn for screening purposes if all relevant laboratory results are not available from within the past 12 months.

Phase 1: Subjects who qualify will be invited for an initial visit during which they will provide informed consent and will be fitted with an ambulatory blood pressure monitor. Subjects will return the next day in a fasting state for a blood draw and spot urine sample, and to return the ambulatory BP monitor. Subjects will then be started on febuxostat, 40 mg, 1 tablet once a day provided by the study investigators.

Phase 2: after 2 months and 4 months on febuxostat therapy, subjects will return for an ambulatory visit during which fasting blood will be drawn for serum uric acid measurement and liver function test evaluation. if liver function tests at either time point are abnormal, (transaminase elevations greater than 3 times the upper limit of normal), subjects will be excluded from further participation. at 2 months after treatment, if serum uric acid is above 6.0 mg/dl, the dose of febuxostat will be increased to 80 mg/day. if serum uric acid is below 6.0 mg/dl, they will continue on the same dose of febuxostat.

Phase 3: Subjects will return after 6 months of febuxostat therapy for a second set of visits for 24hr ambulatory blood pressure measurement, fasting blood and spot urine studies.

Participant Eligibility

Inclusion Criteria: Adult patients (age > 21 years) with gout and hyperuricemia (serum uric acid > 7.0 mg/dl in men and >6.0 mg/dl in women) who are willing to provide informed consent.