Uric Acid and Hypertension in African Americans

NCT00241839 | Completed Phase 3 Results DMC

• 2 other identifiers: 332R01HL079352
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the hypothesis that the administration of a xanthine oxidase inhibitor (allopurinol) will prevent thiazide-induced hyperuricemia, which will result in better blood pressure (BP) control in African Americans.

Conditions

Cardiovascular Diseases; Heart Diseases; Hypertension

Outcome Measures

Primary Outcomes (2)

• Change in Diastolic Blood Pressure by Cuff 8-10 Weeks Minus Baseline

  The Diastolic BP was taken at Baseline and after 8-10 weeks of treatment or placebo while on chlorthalidone and potassium chloride. The blood pressure was measured according to "Shared Care" protocol: 15 minutes of quiet, undisturbed rest with three BP measurements obtained subsequently at 5 minute intervals. The mean of the second and third reading was the value used for analysis for both the Baseline measurement and the measurement after 8 - 10 weeks of treatment. The dependent variable is baseline value minus ending value. Measures are in millimeters of mercury (mm hg)

  Measured at 8-10 weeks on allopurinol / placebo

• Change in Systolic Blood Pressure by Cuff After 8-10 Weeks Minus Baseline

  The systolic BP was taken at Baseline and after 8-10 weeks of treatment on placebo, while on chlorthalidone and potassium chloride. The blood pressure was measured according to "Shared Care" protocol: 15 minutes of quiet, undisturbed rest with three BP measurements obtained subsequently at 5 minute intervals. The mean of the second and third reading was the value used for analysis for both the Baseline measurement and the measurement after 8 - 10 weeks of treatment. The dependent variable is baseline value minus ending value. Measures are in millimeters of mercury (mm hg)

  Measured at 8-10 weeks on allopurinol or placebo

Secondary Outcomes (2)

• Change in Overall Mean BP From Those Obtained by 24 Hour Ambulatory Blood Pressure Measurements (ABPM) 8-10 Weeks Minus Baseline.

  Baseline and end of treatment (8-10 weeks on allopurinol / placebo)

• Change in Uric Acid (UA) Levels: Baseline Less End of Treatment

  Baseline UA levels compared to end of treatment levels (8-10 weeks on allopurinol / placebo)

Study Arms (2)

A

ACTIVE COMPARATOR

Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, Allopurinol 300mg daily was added for 8-10 weeks at which time testing was repeated.

Drug: Allopurinol; Drug: Chlorthalidone; Drug: Potassium chloride

B

PLACEBO COMPARATOR

Chlorthalidone 25 mg and Potassium Chloride 40-50meq were given daily for 5 weeks before baseline visit for testing. After baseline testing was completed, a Placebo,matched in appearance to Allopurinol, was added daily for 8-10 weeks, at which time testing was repeated.

Drug: Placebo; Drug: Chlorthalidone; Drug: Potassium chloride

Interventions

Allopurinol DRUG

Allopurinol (300 mg capsule) was given for 8-10 weeks compared to placebo group after initial baseline testing. After two weeks on the Allopurinol, a serum uric acid level was obtained. If the uric acid level was greater than 5.5, the Allopurinol dosage was increased to 600mg (two 300 mg capsules)for the duration of the trial, 6-8 weeks.

Also known as: Zyloprim

A

Placebo DRUG

Placebo capsule (matched in appearance for Allopurinol and labeled 300mg) was given for 8-10 weeks compared to the Allopurinol group after initial baseline testing. After two weeks on the placebo, a serum uric acid level was obtained. If the uric acid level was greater than 5.5, the placebo dosage was increased to 600mg (two 300 mg capsules)for the duration of the study, 6-8 weeks.

Also known as: sugar pill

B

Chlorthalidone DRUG

Chlorthalidone 25 mg was given daily for 5 weeks before baseline visit for testing and continued through out the study.

A; B

Potassium chloride DRUG

Potassium Chloride 40-50meq was given daily for 5 weeks before baseline visit for testing and continued through out the study.

A; B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• African American (including black individuals born in the Caribbean, Africa, Canada, etc.)
• Are either untreated with any antihypertensive agent, with an average sitting clinic BP of between 140/90 and 159/99 mm Hg OR subjects with hypertension controlled (i.e. BP less than 140/90) or no higher than stage 1 hypertension (i.e., less than 160/100) on a single antihypertensive agent or two antihypertensive agents (individuals on fixed dose ARB-diuretic or ACEI-diuretic combinations will also be considered as being on monotherapy for purposes of the study. Individuals on beta blockade or calcium channel blockade for coronary artery disease and/or arrhythmia will not be eligible for the study)
• Random spot urine protein/creatinine ratio of less than 0.5 (approximates a 24-hour urinary protein excretion of 500 mg/day)
• Calculated MDRD GFR of greater than or equal to 60 ml/min/1.73/m\^2
• No allopurinol or probenecid intake for at least one month prior to study entry
• Willing and able to cooperate with study procedures
• Willing to travel to the GCRC at Shands Hospital for overnight inpatient stays on two separate occasions

You may not qualify if:

• History of malignant or accelerated hypertension
• Confirmed total white cell count of less than 2,500/mm\^3, anemia, or thrombocytopenia
• Known history of liver disease
• Known secondary cause of hypertension
• Known presence of diabetes or fasting blood glucose greater than or equal to 126 mg/dL
• History of heart failure, acute myocardial infarction, or stroke or on a β-blocker or calcium channel blocker for cardiovascular indications other than for lowering blood pressure
• Abnormal EKG requiring medical intervention
• History of clinical or renal biopsy or evidence of renal parenchymal disease
• Acute gout attack within 2 weeks of study entry
• History of drug abuse in the last 2 years, including narcotics, cocaine, or alcohol (greater than 21 drinks/week)
• Arm circumference of greater than 52 cm, which precludes measurement with a 'thigh' BP cuff
• History of a reaction to allopurinol or chlorthalidone
• Pregnant or planning to become pregnant during the study, or breastfeeding
• History of noncompliance, are unable to comply with the study requirements, or who are currently participating in another study
• Not fasting prior to obtaining screening laboratory data. If a participant has clearly not fasted, we will exclude those individuals with casual blood glucose levels of greater than or equal to 200 mg/dL. In the event that a fasting blood sugar exceeds 126 mg/dL, it will be reconfirmed on a blood glucose measurement obtained on a subsequent day, per American Diabetes Association criteria

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (8)

• Johnson RJ, Segal MS, Sautin Y, Nakagawa T, Feig DI, Kang DH, Gersch MS, Benner S, Sanchez-Lozada LG. Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr. 2007 Oct;86(4):899-906. doi: 10.1093/ajcn/86.4.899.

  PMID: 17921363 BACKGROUND

• Nakagawa T, Johnson RJ. Hypertension: Is there a dark side to thiazide therapy for hypertension? Nat Rev Nephrol. 2010 Oct;6(10):564-6. doi: 10.1038/nrneph.2010.114. No abstract available.

  PMID: 20871636 BACKGROUND

• Nakagawa T, Kang DH, Feig D, Sanchez-Lozada LG, Srinivas TR, Sautin Y, Ejaz AA, Segal M, Johnson RJ. Unearthing uric acid: an ancient factor with recently found significance in renal and cardiovascular disease. Kidney Int. 2006 May;69(10):1722-5. doi: 10.1038/sj.ki.5000391.

  PMID: 16598194 BACKGROUND

• Reungjui S, Hu H, Mu W, Roncal CA, Croker BP, Patel JM, Nakagawa T, Srinivas T, Byer K, Simoni J, Wesson D, Sitprija V, Johnson RJ. Thiazide-induced subtle renal injury not observed in states of equivalent hypokalemia. Kidney Int. 2007 Dec;72(12):1483-92. doi: 10.1038/sj.ki.5002564. Epub 2007 Oct 10.

  PMID: 17928827 BACKGROUND

• Reungjui S, Roncal CA, Mu W, Srinivas TR, Sirivongs D, Johnson RJ, Nakagawa T. Thiazide diuretics exacerbate fructose-induced metabolic syndrome. J Am Soc Nephrol. 2007 Oct;18(10):2724-31. doi: 10.1681/ASN.2007040416. Epub 2007 Sep 12.

  PMID: 17855639 BACKGROUND

• Kim KM, Henderson GN, Frye RF, Galloway CD, Brown NJ, Segal MS, Imaram W, Angerhofer A, Johnson RJ. Simultaneous determination of uric acid metabolites allantoin, 6-aminouracil, and triuret in human urine using liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jan 1;877(1-2):65-70. doi: 10.1016/j.jchromb.2008.11.029. Epub 2008 Nov 25.

  PMID: 19081307 BACKGROUND

• Kim KM, Henderson GN, Ouyang X, Frye RF, Sautin YY, Feig DI, Johnson RJ. A sensitive and specific liquid chromatography-tandem mass spectrometry method for the determination of intracellular and extracellular uric acid. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 15;877(22):2032-8. doi: 10.1016/j.jchromb.2009.05.037. Epub 2009 May 27.

  PMID: 19520625 BACKGROUND

• Fravel MA, Ernst ME. Management of gout in the older adult. Am J Geriatr Pharmacother. 2011 Oct;9(5):271-85. doi: 10.1016/j.amjopharm.2011.07.004. Epub 2011 Aug 17.

  PMID: 21849262 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Heart Diseases; Hypertension

Interventions

Allopurinol; Sugars; Chlorthalidone; Potassium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Potassium Compounds

Limitations and Caveats

For all 4 outcomes analyzed, patients required to have data at both baseline and 8-10 weeks on that field to be included. Thus, the numbers of subjects varies slightly from analysis to analysis.

Results Point of Contact

• Title: Mark S. Segal, MD, PhD; Assistant Professor and Chief, Division of Nephrology
• Organization: University of Florida

Mark.Segal@medicine.ufl.edu

352-273-8821

Study Officials

• Mark S. Segal, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2005
• First Posted: October 19, 2005
• Study Start: August 1, 2005
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: July 26, 2013
• Results First Posted: July 17, 2013

Record last verified: 2013-07

Locations

US (1)