Ignite Creation Date:
2025-12-25 @ 2:27 AM
Ignite Modification Date:
2026-03-01 @ 10:02 AM
Study NCT ID:
NCT02472834
Status:
COMPLETED
Last Update Posted:
2021-02-24
First Post:
2015-06-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Trial of Carbamylation in Renal Disease-Modulation With Amino Acid Therapy
Sponsor:
Massachusetts General Hospital
Organization:
Study Overview
Official Title:
Amino Acid Therapy to Modify Protein Carbamylation in End Stage Renal Disease: A Randomized Trial
Status:
COMPLETED
Status Verified Date:
2021-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CarRAAT-2
Brief Summary:
Patients with end stage renal disease (ESRD) usually have high levels of urea that may interact with blood proteins and change their structure by a process known as carbamylation. Evidence suggests that high levels of carbamylated proteins may be linked to adverse outcomes in dialysis patients. This is a randomized, open-label study to evaluate the effects of amino acid supplementation on levels of carbamylated proteins in ESRD patients. Secondary objectives will be to determine whether this intervention can modify intermediate markers of inflammation, cardiac stress, and erythropoietin responsiveness in this population. Sixty ESRD patients on dialysis will be randomized into two groups of 30 patients each. Group 1 will receive intravenous supplementation with an FDA-approved amino acid solution (250 mL of NephrAmine®, 5.4% amino acids) during regular dialysis sessions (3 times weekly for 8 weeks); Group 2 will be treated according to standard-of-care (no amino acid supplementation). During the 8 weeks of therapy and for 4 weeks of follow-up, blood will be drawn from patients' existing hemodialysis access ports (\~20 mL once per month) to measure levels of carbamylated albumin, amino acids, selected biomarkers, and standard laboratory values. Patients randomized to Group 1 will have fluid volume equivalent to the amino acid therapy removed by ultra-filtration to avoid net fluid gain. All patients will be monitored for safety (adverse events) and for changes in hemodynamics and dialysis prescription.
Detailed Description:
As human kidney function declines, so does the kidney's ability to excrete urea, the chief end product of nitrogen metabolism. Excess urea may accelerate the pathophysiological consequences of kidney failure. Urea spontaneously dissociates to form cyanate, which, in its unprotonated form can react with protein amino groups in a process known as carbamylation. Carbamylation-induced protein alterations may be involved in the progression of various diseases by changing the structure, charge, and function of enzymes, hormones, receptors, and amino acids. For example, proteins such as collagen and low density lipoproteins (LDLs), when carbamylated, have been shown to induce the characteristic biochemical events of atherosclerosis progression. This research aims to evaluate whether amino acid supplementation can attenuate such processes that are known to contribute to morbidity in patients with ESRD.
Percent carbamylated albumin (C-Alb) level will be used as a measure of overall carbamylation burden. Previous studies conducted by MGH Investigators have shown a negative correlation between %C-Alb and circulating amino acids, suggesting that free amino acids may actively scavenge reactive isocyanate. Further, ex vivo studies show that amino acid supplementation reduces the carbamylation reaction. The MGH Investigators recently demonstrated an association between markers of cardiac stress, heart failure and carbamylation in patients with ESRD and found that %C-Alb was strongly associated with erythropoietin resistance in dialysis patients. Additionally, using validated measures of total-body carbamylation, these and other Investigators have reported that elevated protein carbamylation was linked with higher mortality in several distinct ESRD cohorts. Finally, preliminary data from a recent pilot study at MGH (NCT01612429) suggests that amino acid supplementation in patients with ESRD undergoing maintenance hemodialysis can attenuate carbamylation of proteins.
The proposed randomized study will directly evaluate the impact of amino acid supplementation on: (1) the burden of carbamylation in terms of %C-Alb; and (2) selected intermediate determinants of clinical outcomes, i.e., markers of inflammation, cardiac stress, and erythropoietin responsiveness.
Percent carbamylated albumin (C-Alb) level will be used as a measure of overall carbamylation burden. Previous studies conducted by MGH Investigators have shown a negative correlation between %C-Alb and circulating amino acids, suggesting that free amino acids may actively scavenge reactive isocyanate. Further, ex vivo studies show that amino acid supplementation reduces the carbamylation reaction. The MGH Investigators recently demonstrated an association between markers of cardiac stress, heart failure and carbamylation in patients with ESRD and found that %C-Alb was strongly associated with erythropoietin resistance in dialysis patients. Additionally, using validated measures of total-body carbamylation, these and other Investigators have reported that elevated protein carbamylation was linked with higher mortality in several distinct ESRD cohorts. Finally, preliminary data from a recent pilot study at MGH (NCT01612429) suggests that amino acid supplementation in patients with ESRD undergoing maintenance hemodialysis can attenuate carbamylation of proteins.
The proposed randomized study will directly evaluate the impact of amino acid supplementation on: (1) the burden of carbamylation in terms of %C-Alb; and (2) selected intermediate determinants of clinical outcomes, i.e., markers of inflammation, cardiac stress, and erythropoietin responsiveness.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 5K23DK106479-04 | NIH | None | https://reporter.nih.gov/quic… | View |