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Trial of Oral Glutamine on Mitochondrial Function in CKD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborators:
New York Medical College
Emory University
Vanderbilt University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Jonathan Himmelfarb, University of Washington

Brief Summary:
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 magnetic resonance spectroscopy and optical spectroscopy (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.

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

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Glutamine

Arm Intervention/treatment
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.
Other Names:
  • CarboMax
  • Dextrin maize starch




Primary Outcome Measures :
  1. Endothelial dysfunction [ Time Frame: 2 weeks ]
    Vascular function as measured by optical spectroscopy

  2. Muscle mitochondrial function [ Time Frame: 2 weeks ]
    Muscle mitochondrial energetics measured by 31P MRS/OS


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults between 20 and 69 years of age
  • Diagnosis of moderate-severe CKD, defined in this study as an estimated glomerular filtration rate (eGFR) of ≤60ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration equation
  • Ability to understand and provide informed consent to participate in the study

Exclusion Criteria:

  • On chronic dialysis
  • Expectation to start dialysis within 6 months or dialysis access in place.
  • Pregnant
  • Have physical immobility (defined by wheelchair use)
  • Insulin dependent diabetes
  • Have implants incompatible with MRI
  • Exercise limiting cardiopulmonary disease (e.g. angina, severe heart valve disease, severe COPD, coronary ischemia)
  • Use of anticoagulation (i.e. warfarin)
  • Baseline systolic blood pressure >160 or diastolic blood pressure >100
  • Inflammatory conditions (e.g. autoimmune disease, HIV)
  • Thyroid disease
  • Dementia or inability to consent
  • Cirrhosis, active/chronic hepatitis
  • Use medications interfering with muscle or mitochondrial function, including steroids, anti-psychotic, Coenzyme Q-10, immunosuppresssives, antivirals, and muscle relaxants
  • Weight >300 lbs
  • Personal history or family history of deep vein thrombosis, pulmonary embolism
  • Active malignancy
  • Patients hospitalized within the past 60 days for any reason.
  • Patients with a history of a major atherosclerotic event (defined as combined incidence of myocardial infarction, urgent target-vessel revascularization, coronary bypass surgery, and stroke) within 3 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): NCT02838979


Contacts
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Contact: Linda Manahan, RN 2066168574 LManahan@Nephrology.washington.edu

Locations
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United States, Washington
Kidney Research Institute, University of Washington Recruiting
Seattle, Washington, United States, 98104
Contact: Bob Roshanravan, MD MS MSPH    206-744-3948    broshanr@uw.edu   
Principal Investigator: Jonathan Himmelfarb, MD         
Sub-Investigator: Bryan Kestenbaum, MD MS         
Sub-Investigator: Bob Roshanravan, MD MS MSPH         
Sponsors and Collaborators
University of Washington
New York Medical College
Emory University
Vanderbilt University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Jonathan Himmelfarb, MD Kidney Research Insitute
Publications:
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Responsible Party: Jonathan Himmelfarb, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT02838979    
Other Study ID Numbers: 47861-A
5K23DK099442 ( U.S. NIH Grant/Contract )
First Posted: July 20, 2016    Key Record Dates
Last Update Posted: July 20, 2016
Last Verified: July 2016
Keywords provided by Jonathan Himmelfarb, University of Washington:
Glutamine
Chronic Kidney Disease
Additional relevant MeSH terms:
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Sarcopenia
Kidney Diseases
Cardiovascular Diseases
Urologic Diseases
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical