Effect of N-Acetylcysteine on Peritoneal Membrane Function in Chronic Peritoneal Dialysis Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2007 by Assaf-Harofeh Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier:
NCT00421785
First received: January 11, 2007
Last updated: July 6, 2007
Last verified: July 2007
  Purpose

The aim of our study is to investigate the effect of N-acetylcysteine on peritoneal small solute clearance and removal of salt and water in prevalent CAPD patients.


Condition Intervention
ESRD
Peritoneal Dialysis
Drug: Oral N-Acetylcysteine 1200 mg x 2/day for 4 weeks.

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of N-Acetylcysteine on Peritoneal Membrane Function in Chronic Peritoneal Dialysis Patients.

Resource links provided by NLM:


Further study details as provided by Assaf-Harofeh Medical Center:

Primary Outcome Measures:
  • dualysis adequacy [ Time Frame: 1 month ]
  • Change in peritoneal small solute transport, measured as adequacy of urea removal – Kt/V.
  • Change in peritoneal ultrafiltration rate on PET test.

Secondary Outcome Measures:
  • Change in residual kidney function
  • Change in Body Weight and Blood Pressure.

Estimated Enrollment: 20
Study Start Date: February 2007
Estimated Study Completion Date: January 2008
Detailed Description:

Cardiovascular disease is the commonest cause of morbidity and mortality in chronic dialysis patients, including those treated with CAPD (Continuous Ambulatory Peritoneal Dialysis) [1]. Uncontrolled arterial hypertension in ESRF leads to progression of LVH, which is a strong predictor for coronary events, CHF and mortality [2]. Fluid overload is a major factor in the pathogenesis of arterial hypertension in CAPD patients [3]. Therefore, interventions to optimize volume status, and hence blood pressure, are considered central in the management of such patients. Such therapies include restricting dietary sodium and water intake, use of diuretics in patients with residual renal function and optimization of peritoneal ultrafiltration with sodium and water removal [1]. As shown in the EAPOS Study, peritoneal ultrafiltration was important predictor of mortality [4].

Peritoneal fluid and salt removal can be increased by using a more hypertonic dialysis fluid using glucose as osmotic agent. Consistent use of hypertonic glucose solutions may damage peritoneal membrane and may also lead to increased systemic absorption of glucose with subsequent hyperglycemia, increased thirst and excessive water drinking. Concerns about the role of glucose in deterioration of peritoneal membrane function have been supported in recent studies [5]. Generally, the evolution of peritoneal membrane properties over time is characterized by a progressive increase in small solute transport, leading to higher glucose absorption rate from peritoneal fluid and loss of ultrafiltration capacity [6]. Such a high peritoneal transport status is associated with less peritoneal fluid removal, overhydration, hypertension and LVH. High peritoneal transport status is a risk factor of mortality in CAPD patients [7].

In recent years, there has been an increasing focus on association between inflammation, increased oxidative stress and high peritoneal transport rate and their relation to mortality in CAPD patients [8 ]. Inflammation has been shown to increase a peritoneal transport rate in CAPD patients [8]. Both inflammation and increased oxidative stress may impact to inadequate fluid removal. The exact mechanism of this phenomenon is not fully understood.

Several experimental and clinical studies showed that increased oxidative stress in dialysis patients may be due to inhibition of nitric oxide (NO) synthesis by ADMA (Asymmetric Dimethylarginine ), known to be endogenous inhibitor of NO synthetase [9]. ADMA may be significantly reduced by dialysis [10]. Metabolism of ADMA is primarily by the enzyme DDAH , which activity is decreased by inflammation, oxidative stress, diabetes mellitus and hypercholesterolemia [11]. It was proposed that circulating ADMA may be one mechanism accounting for the resistant hypertension and fluid overload in dialysis patients [11].

Based on current knowledge, treatment aimed at reducing oxidative stress should decrease ADMA levels [11], and it is logical to suggest that such a therapy might improve BP control and fluid status in CAPD patients. In our opinion, it is worth to check an ability of antioxidant therapy to produce a favorable effect on biological properties of peritoneal membrane. One preliminary study on effect of antioxidant Vitamin E showed a small beneficial effect on ADMA in chronic kidney disease [12].

N-Acetylcysteine (NAC) is an active antioxidant proved to be safe and beneficial in hemodialysis patents [13]. In our recent study, NAC effectively reduced the ototoxic effect of gentamicin in chronic hemodialysis patients [14].

The aim of our study is to investigate the effect of N-acetylcysteine on peritoneal small solute clearance and removal of salt and water in prevalent CAPD patients.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The study will include 20 patients with ESRD, treated with chronic peritoneal dialysis .

Exclusion Criteria:

  • Recently started treated with chronic dialysis: less than 3 months.
  • Survived recent peritonitis in the last 3 months.
  • Patients with acute renal failure
  • Currently treated with antioxidants ( NAC, vitamin E ets.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00421785

Contacts
Contact: Leonid S Feldman, MD +972-8-9779383 leonidf@asaf.health.gov.il

Locations
Israel
Dialyss unit Recruiting
Zerifin, Israel, 70300
Contact: Leonid s Feldman    +972-8-9779383    leonidf@asaf.health.gov.il   
Sponsors and Collaborators
Assaf-Harofeh Medical Center
Investigators
Principal Investigator: Leonid S Feldman, MD Assaf Harofeh MC
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00421785     History of Changes
Other Study ID Numbers: 346147CTIL
Study First Received: January 11, 2007
Last Updated: July 6, 2007
Health Authority: Israel: Ministry of Health

Keywords provided by Assaf-Harofeh Medical Center:
N-acetylcysteine
Peritoneal Dialysis
ADMA

Additional relevant MeSH terms:
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on July 31, 2014