Trial of Oral Glutamine on Mitochondrial Function in CKD
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|ClinicalTrials.gov Identifier: NCT02838979|
Recruitment Status : Unknown
Verified July 2016 by Jonathan Himmelfarb, University of Washington.
Recruitment status was: Recruiting
First Posted : July 20, 2016
Last Update Posted : July 20, 2016
|Condition or disease||Intervention/treatment||Phase|
|Cardiovascular Disease Sarcopenia Endothelial Dysfunction Muscle Mitochondrial Function Kidney Disease||Dietary Supplement: L-glutamine Dietary Supplement: Maltodextrin||Phase 2|
Chronic kidney disease is associated with endothelial cell dysfunction and muscle wasting contributing to the heightened risk of cardiovascular morbidity, mortality and functional limitation. Accumulation of toxins in renal disease may adversely impact endothelial cell nitric oxide bioavailability and endothelial Nitric Oxide Synthase (eNOS) function consequently heightening oxidative stress and suppressing mitochondrial biogenesis. To date no studies have investigated potential therapies for endothelial and muscle dysfunction in renal disease target mitochondrial metabolic and energetic processes.
Animal studies of uremia underscore mitochondrial dysfunction as a potential precursor for endothelial dysfunction. In particular, uremia has been linked to a proteomic signature indicative of metabolic blockage of TCA cycle activity and fatty acid beta-oxidation. Both of these processes are localized to the mitochondria and may suggest that decreased mitochondrial mass or function may augur endothelial dysfunction in renal disease.
Glutamine, an anaplerotic agent and precursor to the antioxidant glutathione, is a potential therapeutic agent bypassing the metabolic block associated with reduced TCA cycle and improving antioxidant reserve. The primary goal of proposed investigation is to study the impact of oral glutamine supplementation on muscle mitochondrial and endothelial cell function measured mitochondrial energetics and vascular function using 31P MRS/OS among persons with moderate-severe CKD. The secondary objective is to describe the impact of oral glutamine supplementation on mitochondrial metabolic profile as well as inflammatory and oxidative stress biomarkers among persons with chronic kidney disease.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Triple (Participant, Care Provider, Outcomes Assessor)|
|Official Title:||Randomized Cross-over Trial of Oral L-Glutamine vs Maltodextrin on Mitochondrial Function in Chronic Kidney Disease|
|Study Start Date :||July 2015|
|Estimated Primary Completion Date :||June 2017|
|Estimated Study Completion Date :||September 2017|
Experimental: Oral L-Glutamine (0.4mg/kg/day)
Subjects will receive 0.4 g/kg/day of L-glutamine (Nutrestore, EMMAUS Life Sciences, Inc Torrance, CA) in three divided daily doses. Duration 2 weeks
Dietary Supplement: L-glutamine
Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
Other Name: Nutrestore, EMMAUS Life Sciences, Inc Torrance, CA
Placebo Comparator: Maltodextrin
Identical appearing maltodextrin powder.
Dietary Supplement: Maltodextrin
Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
- Endothelial dysfunction [ Time Frame: 2 weeks ]Vascular function as measured by optical spectroscopy
- Muscle mitochondrial function [ Time Frame: 2 weeks ]Muscle mitochondrial energetics measured by 31P MRS/OS
- Change in urine albumin excretion in active agent vs. placebo [ Time Frame: 2 weeks ]To test if glutamine reduces albuminuria by comparing the test results from each arm.
- Percent change in ratio (poise) of thiol/disulfide couples in vivo in active agent vs placebo [ Time Frame: 2 weeks ]To test if glutamine reduces oxidative stress by comparing the measurement of poise of thiol/disulfide couples in vivo from each arm.
- Change in CRP results in active agent vs. placebo [ Time Frame: 2 weeks ]To test if glutamine reduces inflammatory by comparing the measurement of CRP results from each arm.
- Change in force-time integral area under the curve in active agent vs. placebo [ Time Frame: 2 weeks ]To test if glutamine improves objective isometric muscle fatigue by comparing the measurement of FTI from each arm.
- Change in 24-hour urine urea nitrogen in active agent vs. placebo [ Time Frame: 2 weeks ]To test if glutamine improves nitrogen balance by comparing the measurement of 24-hour urine urea nitrogen from each arm.
- Change in eGFR in active agent vs. placebo. [ Time Frame: 2 weeks ]To test if glutamine improves a serum chemistry marker of kidney function by comparing the measurement of eGFR from each arm.
- Change in pattern of mitochondrial metabolism cycling in active agent vs. placebo. [ Time Frame: 2 weeks ]To test if glutamine affects mitochondria metabolism by comparing the pattern described by the analysis of mitochondrial metabolites from each arm.
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): NCT02838979
|Contact: Linda Manahan, RN||2066168574||LManahan@Nephrology.washington.edu|
|United States, Washington|
|Kidney Research Institute, University of Washington||Recruiting|
|Seattle, Washington, United States, 98104|
|Contact: Bob Roshanravan, MD MS MSPH 206-744-3948 firstname.lastname@example.org|
|Principal Investigator: Jonathan Himmelfarb, MD|
|Sub-Investigator: Bryan Kestenbaum, MD MS|
|Sub-Investigator: Bob Roshanravan, MD MS MSPH|
|Principal Investigator:||Jonathan Himmelfarb, MD||Kidney Research Insitute|