Cardiovascular DiseasePhase 2NCT02838979

Trial of Oral Glutamine on Mitochondrial Function in CKD

A Phase 2 study testing First Intervention (14 days), Washout (3 weeks) and Second Intervention (14 days) in people with Cardiovascular Disease and Sarcopenia, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 20 to 69 years
Conditions the study is for: Cardiovascular Disease, Sarcopenia, Endothelial Dysfunction
What is being tested?: First Intervention (14 days), Washout (3 weeks) and Second Intervention (14 days)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteUnited States
Study dates: 25 Feb 2016to 31 Jan 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 69 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 19Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Kidney Research Institute, University of Washington
Seattle, Washington, 98104

Other trials in United States

About this study

Official title: Randomized Cross-over Trial of Oral L-Glutamine vs Maltodextrin on Mitochondrial Function in Chronic Kidney Disease

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.

Read the 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.

Conditions: Cardiovascular Disease, Sarcopenia, Endothelial Dysfunction, Muscle Mitochondrial Function, Kidney Disease
Being tested: First Intervention (14 days), Washout (3 weeks), Second Intervention (14 days)
Keywords: Glutamine, Chronic Kidney Disease
Medical subject headings: Cardiovascular Diseases, Sarcopenia, Kidney Diseases, Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

First Intervention (14 days)Dietary supplement
Oral Glutamine or Maltodextrin for 2 weeks
Washout (3 weeks)Other
No study product is taken prior to beginning crossover
Second Intervention (14 days)Dietary supplement
Oral Glutamine or Maltodextrin for 2 weeks

Study groups in NCT02838979
Study group	Role	What they receive
Oral L-Glutamine first, then Maltodextrin	Experimental	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 Receives: Dietary Supplement: First Intervention (14 days); Other: Washout (3 weeks); Dietary Supplement: Second Intervention (14 days)
Maltodextrin first, then L-glutamine	Experimental	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 Receives: Dietary Supplement: First Intervention (14 days); Other: Washout (3 weeks); Dietary Supplement: Second Intervention (14 days)

What is being measured

The primary outcome is the main question the study is designed to answer.

Muscle Mitochondrial Function
31P MRS/OS was used to measure mitochondrial phosphorylation capacity (ATPmax).
Measured: 2 weeks

Secondary outcomes (2)

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),
Measured: 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.
Measured: 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Feb 201631 Jan 2018

First posted20 Jul 2016 (estimated)
Study start25 Feb 2016
Primary completion1 Oct 2017
Study completion31 Jan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
More trials run by University of WashingtonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Outcomes assessor
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02838979
Sponsor's protocol ID: 47861
Other IDs: 5K23DK099442
Status last verified: Mar 2022
First submitted: 8 Jul 2016
Last updated: 14 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari-Baliviera E, Lowe DK, Wilmore DW. Safety and metabolic effects of L-glutamine administration in humans. JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):137S-146S. doi: 10.1177/0148607190014004201.
PubMed 2119459
Amara CE, Marcinek DJ, Shankland EG, Schenkman KA, Arakaki LS, Conley KE. Mitochondrial function in vivo: spectroscopy provides window on cellular energetics. Methods. 2008 Dec;46(4):312-8. doi: 10.1016/j.ymeth.2008.10.001. Epub 2008 Oct 16.
PubMed 18930151
Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med. 2009 Nov 15;47(10):1329-38. doi: 10.1016/j.freeradbiomed.2009.08.021. Epub 2009 Aug 26.
PubMed 19715755

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)

All Cardiovascular Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Cross-over Trial of Oral L-Glutamine vs Maltodextrin on Mitochondrial Function in Chronic Kidney Disease
ClinicalTrials.gov ID: NCT02838979
Acronym / sponsor ID: 47861
Conditions: Cardiovascular Disease, Sarcopenia, Endothelial Dysfunction, Muscle Mitochondrial Function, Kidney Disease
Keywords: Glutamine, Chronic Kidney Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: University of WashingtonUniversity, hospital or other
Collaborators: New York Medical College, Emory University, Vanderbilt University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: 25 Feb 2016 (actual)
Primary completion: 1 Oct 2017 (actual)
Study completion: 31 Jan 2018 (actual)
First posted: 20 Jul 2016 (estimated)
Results: Posted 14 Jul 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Oral L-Glutamine first, then Maltodextrin	Experimental	Dietary Supplement: First Intervention (14 days), Other: Washout (3 weeks), Dietary Supplement: Second Intervention (14 days)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
Maltodextrin first, then L-glutamine	Experimental	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

Who may qualify

Ages: 20 to 69 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (19 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
First Intervention (14 days)Oral Glutamine or Maltodextrin for 2 weeks	Dietary supplement	Maltodextrin first, then L-glutamine, Oral L-Glutamine first, then Maltodextrin
Washout (3 weeks)No study product is taken prior to beginning crossover	Other	Maltodextrin first, then L-glutamine, Oral L-Glutamine first, then Maltodextrin
Second Intervention (14 days)Oral Glutamine or Maltodextrin for 2 weeks	Dietary supplement	Maltodextrin first, then L-glutamine, Oral L-Glutamine first, then Maltodextrin

Primary outcome

Muscle Mitochondrial Function
Time frame: 2 weeks
31P MRS/OS was used to measure mitochondrial phosphorylation capacity (ATPmax).

2 secondary outcomes

Change in Force-time Integral Area Under the Curve in Active Agent vs. Placebo
Time frame: 2 weeks
Muscle Fatigue
Time frame: 2 weeks

Results and safety

Results posted to the registry on 14 Jul 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Oral L-Glutamine First, Then Maltodestrin	6	6
Maltodextrin First, Then L-glutamine	5	5

Primary outcome: Muscle Mitochondrial Function

Time frame: 2 weeks. Mean (Standard Deviation). Unit: mM ATP/s

Measure	L-Glutamine n = 11	Maltodextrin n = 11
Value	0.88 (0.30)	0.90 (0.34)

L-Glutamine vs Maltodextrin: Mean Difference (Final Values): -0.01, p = 0.15, ANOVA

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 7 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
L-Glutamine	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Maltodextrin	0 of 11 (0%)	0 of 11 (0%)	0 of 11

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 2119459Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari-Baliviera E, Lowe DK, Wilmore DW. Safety and metabolic effects of L-glutamine administration in humans. JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):137S-146S. doi: 10.1177/0148607190014004201.
Background: PubMed 18930151Amara CE, Marcinek DJ, Shankland EG, Schenkman KA, Arakaki LS, Conley KE. Mitochondrial function in vivo: spectroscopy provides window on cellular energetics. Methods. 2008 Dec;46(4):312-8. doi: 10.1016/j.ymeth.2008.10.001. Epub 2008 Oct 16.
Background: PubMed 19715755Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med. 2009 Nov 15;47(10):1329-38. doi: 10.1016/j.freeradbiomed.2009.08.021. Epub 2009 Aug 26.

Related trials for Cardiovascular Disease

Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jonathan Himmelfarb, MD principal investigator

Kidney Research Insitute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Muscle Mitochondrial Function (time frame: 2 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02838979, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2022.