Trial record 6 of 74 for:
Recruiting, Not yet recruiting, Available Studies | "Nephrolithiasis"
Pathophysiology of Uric Acid Nephrolithiasis (IUAN)
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| ClinicalTrials.gov Identifier: NCT00904046 |
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Recruitment Status :
Recruiting
First Posted : May 19, 2009
Last Update Posted : May 22, 2018
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Sponsor:
University of Texas Southwestern Medical Center
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Khashayar Sakhaee, University of Texas Southwestern Medical Center
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Brief Summary:
This study has two aims:
Aim 1: To determine the presence of accumulation of fat within cells and the functional consequences of this in the kidney by correlating kidney fat content with urine test results.
Aim 2: The investigators will evaluate the effect of thiazolidinedione (pioglitazone) on excess fatty acid accumulation in kidney tissue and its correlation with uric acid stone formation in subjects with uric acid stones.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Uric Acid Kidney Stone Disease | Drug: Pioglitazone Drug: Placebo | Not Applicable |
The study will use a combination of cell culture, animal, and human studies employing some of the latest technologies in magnetic resonance spectroscopy and single-photon emission computed tomography, combined with classical physiology, biochemistry, and molecular biology to test four interrelated hypotheses. There is increased uptake of free fatty acids into the kidney as a result of higher circulating levels as well as preferential transport by the proximal tubule as part of a "conditioning" effect. The increased provision of free fatty acid supplies metabolic substrate for ATP generation hence reducing the consumption of other substrates such as glutamine, which is the principal source of ammoniagenesis by the proximal tubule. This substrate competition, or metabolic switch, can lower the formation of the major urinary buffer ammonia, even in the absence of injury to the proximal tubule. With sustained lipid loading of the proximal tubule that exceeds its oxidative capacity, lipid storage is first activated but with time, toxic lipid metabolites may build up. We have evidence that excess saturated fat, which is prevalent in the Western diet, leads to proximal tubule lipotoxicity manifested as endoplasmic reticulum (ER) leakage/stress, and we propose that defective ammoniagenesis is part of a broader lipotoxic phenotype. We further propose that accumulation of a specific lipid species may be responsible for the toxicity. To test whether proximal tubule steatosis and lipotoxicity in humans have a functional consequence, we will study uric acid stone formers. Having previously shown that thiazolidinediones (TZD) reduce renal steatosis and lipotoxicity and improve ammonium excretion in animals, we have initiated a randomized intervention trial with TZD or placebo in human uric acid stone formers. The interim analysis showed that after 6 months of TZD therapy, stone formers had improved urinary biochemical parameters and reduced propensity for uric acid precipitation. We will continue this trial but add a novel highly sensitive method to non-invasively measure renal fat, testing whether improvement in urinary biochemistry associates with reduction of renal fat. This proposal addresses fundamental concepts of renal tubular lipid biology and lipotoxicity, and clinically will shift the paradigm of uric acid stone therapy from empiric urinary alkalinization to specific reduction in renal fat. We will also introduce cutting-edge human imaging studies for kidney research.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Basic Science |
| Official Title: | Pathophysiology of Uric Acid Nephrolithiasis |
| Study Start Date : | May 2009 |
| Estimated Primary Completion Date : | April 2019 |
| Estimated Study Completion Date : | December 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Kidney Stones
| Arm | Intervention/treatment |
|---|---|
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Experimental: Pioglitazone
For 60 Aim 2 Subjects Only - Pioglitazone (Actos)
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Drug: Pioglitazone
30 mg orally daily for 6 months
Other Name: Thiazolidinedione |
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Placebo Comparator: Placebo
For 60 Subjects in Aim 2 Only - Placebo for Pioglitazone
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Drug: Placebo
Placebo taken orally once a day for 6 months. |
Primary Outcome Measures :
- Reversal of renal lipotoxicity will occur with pioglitazone. [ Time Frame: 6 months ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 21 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Subjects with uric acid kidney stone disease
- Age > 21 years
Exclusion Criteria:
- Body weight> 350 lb
- Chronic alcohol use
- Chronic liver disease
- Chronic renal disease
- Anemia
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Contraindication to pioglitazone use:
- history of congestive heart failure NYHA class III or IV
- significant pedal edema
- liver failure
- not willing to practice an effective contraception for the duration of the study
- Thiazolidinedione use in the preceding 18 months
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00904046
Contacts
| Contact: Ann Heard-Sakhaee, RN | 214-648-4893 | Ann.Heard-Sakhaee@UTSouthwestern.edu | |
| Contact: Marsha Roberts, RN | 214-648-0399 | marsha.roberts@UTSouthwestern.edu |
Locations
| United States, Texas | |
| UT Southwestern Medical Center - Center for Mineral Metabolism | Recruiting |
| Dallas, Texas, United States, 75390-8885 | |
Sponsors and Collaborators
University of Texas Southwestern Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Takeda Pharmaceuticals North America, Inc.
Investigators
| Principal Investigator: | Khashayar Sakhaee, MD | UT Southwestern |
Additional Information:
| Responsible Party: | Khashayar Sakhaee, Professor of Internal Medicine, University of Texas Southwestern Medical Center |
| ClinicalTrials.gov Identifier: | NCT00904046 History of Changes |
| Other Study ID Numbers: |
00000125 - 856 1R01DK081423 ( U.S. NIH Grant/Contract ) |
| First Posted: | May 19, 2009 Key Record Dates |
| Last Update Posted: | May 22, 2018 |
| Last Verified: | May 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
Keywords provided by Khashayar Sakhaee, University of Texas Southwestern Medical Center:
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Uric acid Nephrolithiasis |
Additional relevant MeSH terms:
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Kidney Calculi Nephrolithiasis Kidney Diseases Urologic Diseases Urolithiasis Urinary Calculi Calculi Pathological Conditions, Anatomical |
Pioglitazone Uric Acid Hypoglycemic Agents Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents |