Carbamylation in Renal Disease-modulation With Amino Acid Therapy

NCT01612429 | Completed Early Phase 1

• 2 other identifiers: 2012-P-000775IRB# 12-303
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to evaluate the effects of amino acid supplementation on the structure of certain proteins in the blood of dialysis patients. 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. The investigators are interested in determining whether carbamylation is linked to adverse outcomes in dialysis patients and have hypothesized that supplementation with a balanced formulation of amino acids can reduce the amount of carbamylation that occurs. In this study, dialysis patients (n= up to 30) will receive intravenous supplementation with an FDA-approved amino acid solution (NephrAmine®, 5.4% amino acids) during regular dialysis sessions (3 times weekly for 6 weeks). During the 6 weeks of therapy and for 2 weeks of follow-up, blood will be drawn from patients' existing hemodialysis access ports (\~60 ml total per month) to measure levels of carbamylated albumin, amino acids, and standard laboratory values. Patients will be closely monitored for safety and tolerability of the amino acid therapy. For each treated subject, we will follow an additional individual that is not receiving treatment to serve as a control (no intervention).

Conditions

End Stage Renal Failure on Dialysis

Keywords

Carbamylation; Albumin; Protein structure; Kidney disease

Outcome Measures

Primary Outcomes (1)

• Change from baseline in plasma carbamylated albumin levels

  Baseline and 6 weeks

Secondary Outcomes (1)

• Number of patients with adverse events

  8 weeks

Study Arms (1)

Amino acid supplementation

EXPERIMENTAL

Up to 500 mL of 5.4% amino acid solution (NephrAmine) by intravenous infusion 3 x weekly for 6 weeks.

Dietary Supplement: Amino acid supplementation

Interventions

Amino acid supplementation DIETARY_SUPPLEMENT

Single arm study in which dialysis patients will receive up to 500 mL of NephrAmine® (5.4% amino acids for injection; B. Braun Medical, Inc) containing 26.8 grams of essential amino acids at 125 mL/h during each dialysis session (3 times weekly for 6 weeks)

Also known as: NephrAmine®

Amino acid supplementation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed of the investigational nature of the study and sign written informed consent
• Willing and able to adhere to all study-related procedures, including adherence to study medication regimen
• ≥18 years old
• On stable medical therapy in the last 30 days before the study entry, defined as no change, addition, or removal of medications
• Patients must satisfy the following criteria based on the initial screening laboratory values:
• Serum albumin ≥ 3.0 g/dL (30 g/L)
• Dialysis adequacy recorded as Kt/ V \> 1.2
• Women of childbearing potential must be practicing barrier or oral contraception, for the duration of the study-related treatment, or be documented as surgically sterile or one year post-menopausal
• If female, be non-nursing, non-pregnant and have a negative pregnancy test within two weeks of starting study treatment
• On stable hemodialysis therapy for at least 90 days before the study entry, defined as receiving thrice weekly dialysis and carrying a diagnosis of ESRD
• Prescribed a dialysis treatment time of 4 hours per session

You may not qualify if:

• Taking any type of amino acid supplementation within the last 90 days
• Received parenteral nutrition within last 90 days
• History of allergy to any amino acid compound
• Poorly controlled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 110 mmHg during any of the previous 3 dialysis sessions (confirmed by repeat)
• Severe hepatic impairment
• Condition with prognosis \<1 year at time of study entry
• Current active treatment in another investigational study or participation in another investigational study in the 1 month prior to screening
• Active malignancies or other serious concurrent or recent medical or psychiatric condition which, in the opinion of the Investigator, makes the patient unsuitable for participation in this study

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Kalim S, Ortiz G, Trottier CA, Deferio JJ, Karumanchi SA, Thadhani RI, Berg AH. The Effects of Parenteral Amino Acid Therapy on Protein Carbamylation in Maintenance Hemodialysis Patients. J Ren Nutr. 2015 Jul;25(4):388-92. doi: 10.1053/j.jrn.2015.01.019. Epub 2015 Mar 5.

  PMID: 25753604 RESULT

MeSH Terms

Conditions

Kidney Diseases

Interventions

Amino Acids, Essential

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Ravi Thadhani, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research in Nephrology

Study Record Dates

• First Submitted: May 31, 2012
• First Posted: June 5, 2012
• Study Start: January 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: November 10, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)