A Phase 2 interventional study of First Intervention (14 days) and Washout (3 weeks) in Cardiovascular Disease, Sarcopenia and Endothelial Dysfunction, sponsored by University of Washington. Completed at 1 site in United States. Open to participants aged 20 Years to 69 Years. Per ClinicalTrials.gov, last updated 2022-07-14.
Sponsored by University of Washington · Phase 2, Interventional, and Treatment
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.
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.
5,025 studies on the registry are indexed under Cardiovascular Diseases; 930 are open to participants now.
This study's enrollment of 11 is below the median of 100 across 2,801 interventional studies indexed under Cardiovascular Diseases.
Browse Cardiovascular Diseases studies →University of Washington is the lead sponsor of 1,431 studies on the registry; 226 are open to participants now.
Of its 158 completed or terminated interventional studies of FDA-regulated products, 136 (86%) have results posted.
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Exclusion Criteria:
Subjects will receive 0.4 g/kg/day of L-glutamine (Nutrestore, EMMAUS Life Sciences, Inc Torrance, CA) in three divided daily doses OR identical appearing maltodextrin powder. Duration 2 weeks
Dietary Supplement: First Intervention (14 days) · Other: Washout (3 weeks) · Dietary Supplement: Second Intervention (14 days)
Subjects will crossover to receiving the study product which they did not receive in the first period. Either 0.4 g/kg/day of L-glutamine in three divided daily doses OR identical appearing maltodextrin powder. Duration 2 weeks
Dietary Supplement: First Intervention (14 days) · Other: Washout (3 weeks) · Dietary Supplement: Second Intervention (14 days)
Oral Glutamine or Maltodextrin for 2 weeks
No study product is taken prior to beginning crossover
Oral Glutamine or Maltodextrin for 2 weeks
Muscle Mitochondrial Function
31P MRS/OS was used to measure mitochondrial phosphorylation capacity (ATPmax).
Time frame: 2 weeks
Change in Force-time Integral Area Under the Curve in Active Agent vs. Placebo
To test if glutamine improves objective isometric muscle fatigue by comparing the measurement of FTI from each arm. Muscle fatigability was tested by calculating FTI as the area under the force-time curve during isometric force generated at 70 % of maximal voluntary contraction (MVC),
Time frame: 2 weeks
Muscle Fatigue
To test the effect of glutamine supplementation on muscle endurance, sum of the muscle force (force-time integral, FTI, N\*s) normalized to maximum voluntary contraction (MVC, N) generated during voluntary contraction.
Time frame: 2 weeks
Plasma NAD+ Levels
To test if glutamine improves plasma NAD+ compared to placebo. Plasma NAD+ concentrations were quantified in mM using 31p MRS based in vivo assay.
Time frame: 2 weeks
| Milestone | Oral L-Glutamine First, Then Maltodestrin | Maltodextrin First, Then L-glutamine |
|---|---|---|
| Started | 6 | 5 |
| Completed | 6 | 5 |
| Not completed | 0 | 0 |
31P MRS/OS was used to measure mitochondrial phosphorylation capacity (ATPmax).
| mM ATP/s | L-Glutamine | Maltodextrin |
|---|---|---|
| Muscle Mitochondrial Function | 0.88 ± 0.30 | 0.90 ± 0.34 |
To test if glutamine improves objective isometric muscle fatigue by comparing the measurement of FTI from each arm. Muscle fatigability was tested by calculating FTI as the area under the force-time curve during isometric force generated at 70 % of maximal voluntary contraction (MVC),
| N*s | L-Glutamine | Maltodextrin |
|---|---|---|
| Change in Force-time Integral Area Under the Curve in Active Agent vs. Placebo | 58.87 ± 24.07 | 52.36 ± 21.22 |
To test the effect of glutamine supplementation on muscle endurance, sum of the muscle force (force-time integral, FTI, N\*s) normalized to maximum voluntary contraction (MVC, N) generated during voluntary contraction.
| s-1 | L-Glutamine | Maltodextrin |
|---|---|---|
| Muscle Fatigue | 2.52 ± 1.09 | 2.41 ± 1.03 |
To test if glutamine improves plasma NAD+ compared to placebo. Plasma NAD+ concentrations were quantified in mM using 31p MRS based in vivo assay.
| mM | L-Glutamine | Maltodextrin |
|---|---|---|
| Plasma NAD+ Levels | 0.95 ± 0.25 | 0.98 ± 0.19 |
To test if glutamine improves maximal voluntary contraction compared to placebo. Maximum voluntary contraction (MVC) was determined by the isometric force generated using first dorsal interosseous (FDI) muscle against a force transducer.
| N/m | L-Glutamine | Maltodextrin |
|---|---|---|
| Maximal Voluntary Contraction | 23.6 ± 6.834 | 23.22 ± 8.967 |
Collected over 7 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| L-Glutamine | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
| Maltodextrin | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
| Age, Continuous(years) | L-Glutamine First, Then Maltodextrin | Maltodextrin First, Then L-glutamine | Total |
|---|---|---|---|
| Mean | 57 ± 16.6 | 58 ± 9.8 | 58 ± 13.3 |
| Sex: Female, Male(Participants) | L-Glutamine First, Then Maltodextrin | Maltodextrin First, Then L-glutamine | Total |
|---|---|---|---|
| Female | 4 | 1 | 5 |
| Male | 2 | 4 | 6 |
| Ethnicity (NIH/OMB)(Participants) | L-Glutamine First, Then Maltodextrin | Maltodextrin First, Then L-glutamine | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 6 | 5 | 11 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | L-Glutamine First, Then Maltodextrin | Maltodextrin First, Then L-glutamine | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 2 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 5 | 3 | 8 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | L-Glutamine First, Then Maltodextrin | Maltodextrin First, Then L-glutamine | Total |
|---|---|---|---|
| United States | 6 | 5 | 11 |
Documents are hosted by the registry — open the source record to download them.
Ran from Feb 2016 to primary completion in Oct 2017, 19 months.
Results were first posted in Jul 2022, 4 years 9 months after primary completion.
Of 54 non-industry phase 2 interventional studies under Cardiovascular Diseases, half reached primary completion within 40 months of starting (the median), counting those still running; a quarter within 24 and three quarters within 73. This study's 19 months is below that.
Counting every sponsor, half of 76 studies reached it within 28 months; a quarter within 18 and three quarters within 57.
Cardiovascular Diseases covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
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