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Metabolic Acidosis in Renal Transplant Patients (MART)

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ClinicalTrials.gov Identifier: NCT00913796
Recruitment Status : Completed
First Posted : June 4, 2009
Last Update Posted : October 22, 2010
Sponsor:
Collaborators:
University of Texas Southwestern Medical Center
Swiss Federal Institute of Technology
Information provided by:
University of Zurich

Tracking Information
First Submitted Date  ICMJE April 1, 2009
First Posted Date  ICMJE June 4, 2009
Last Update Posted Date October 22, 2010
Study Start Date  ICMJE December 2007
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2009)
Correction of metabolic acidosis [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2009)
Improvement in physical capacity [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Metabolic Acidosis in Renal Transplant Patients
Official Title  ICMJE Metabolic Acidosis and Its Impact on Mineral Metabolism and Physical Performance in Renal Transplant Patients
Brief Summary

Acidosis (accumulation of acid in the body) may be an underrecognized problem in patients after renal transplantation. It may have consequences on physical performance due to negative effects on bone and muscle metabolism.

Therefore, the purpose of this study is

  1. to determine the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis
  2. to study the effect of substituting base equivalents (citrate) on acid/base status of renal transplant patients with acidosis
  3. to compare the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis before and after substitution with citrate
Detailed Description

Chronic kidney disease is developing to become one of the major health problems in the Western world with more than one million patients on renal replacement therapy, and many more expected in the years ahead [1]. Survival of patients with end stage renal disease has become possible with the introduction of dialysis therapy. Renal transplantation has resulted both in further reduction of mortality and improvement in quality of life for patients with end stage renal disease. Nevertheless, successful transplantation with regard to graft and patient survival is still associated with significant morbidity. Apart from infectious complications and cardiovascular disease, limitations in physical capacity from musculoskeletal disorders have become a relevant problem, resulting in reduced quality of life, poor physical functioning and inability to work.

Muscle and bone metabolism in chronic kidney disease are typically disturbed resulting in significant pathology and dysfunction of the affected tissues. They are associated with metabolic disorders related to renal insufficiency, among which metabolic acidosis is a major contributor. Metabolic acidosis is a well recognized problem in renal transplant patients. However, its prevalence, pathogenesis, course and sequelae are not well established. In particular, its relation to post-transplant bone and muscle disorders, and the impact on physical capabilities in renal transplant patients have not been comprehensively investigated so far.

The purpose of the proposed project is to examine the characteristics and pathogenesis of post-transplant metabolic acidosis, and its relation to bone and muscle pathologies and impact on physical capabilities in renal transplant patients. In particular, the following aims are proposed to investigate in de novo and long-term renal transplantation:

Aim # 1: To examine the type, degree and course of metabolic acidosis in renal transplant patients, early and long-term after transplantation

Aim # 2: To examine alterations in mineral and bone metabolism, and bone structure, and their relationship to the acid/base disorder

Aim # 3: To examine overall physical performance, exercise capacity and muscle energy content, and their relationship to the acid/base disorder

In order to analyze secondary effects of subclinical and overt acidosis on bone (Aim # 2) and muscle (Aim # 3), patients will be studied at baseline, and then be supplemented with base equivalents in order to achieve a stable plasma serum bicarbonate concentration of 24-26 mmol/l, and be reexamined thereafter. Completion of the three aims will allow to comprehensively analyze the pathogenesis of and interrelations between acid/base status, mineral metabolism, bone disorders and muscle function in renal transplant patients. This will be the first study to link metabolic alterations to structural and functional measures of the musculoskeletal system, and to the impact of the resulting pathologies on physical disabilities in patients with a kidney graft. We are in dire need to know the magnitude of the problem, whether to treat, and how aggressive to treat these patients. The results of this project will be indispensable regarding justification to rigorously evaluate and treat metabolic acidosis in patients with chronic renal insufficiency and after transplantation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Transplant Patients
  • Metabolic Acidosis
  • Physical Capacity
  • Bone Disease
  • Mineral Metabolism
Intervention  ICMJE
  • Drug: Potassium citrate
    2.41 gram of citrate b.i.d. for 12 months. Dosage to be adjusted according to serum potassium concentration.
  • Drug: Potassium chloride
    370 mg potassium t.i.d. for 12 months. Dosage to be adjusted according to serum postassium concentration.
Study Arms  ICMJE
  • Experimental: Postassium citrate
    Aim: correction of metabolic acidosis
    Intervention: Drug: Potassium citrate
  • Active Comparator: Potassium chloride
    Potassium chloride is given to compensate for any possible effects of potassium in potassium citrate (primary treatment).
    Intervention: Drug: Potassium chloride
Publications * Starke A, Corsenca A, Kohler T, Knubben J, Kraenzlin M, Uebelhart D, Wüthrich RP, von Rechenberg B, Müller R, Ambühl PM. Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality. Clin J Am Soc Nephrol. 2012 Sep;7(9):1461-72. Epub 2012 Jul 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 3, 2009)
30
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2010
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with a renal graft having been transplanted within the previous 8 years and being at least 3 months post transplantation, or, patients scheduled to undergo transplantation from a living organ donor within the upcoming 3 months
  • Venous serum bicarbonate concentration < 24 mmol/L at time of baseline determination
  • Renal transplant function with a calculated glomerular filtration rate (GFR) greater or equal 30 ml/min according to the Cockcroft-Gault formula
  • Immunosuppressive therapy including a calcineurin inhibitor (cyclosporine A or tacrolimus)
  • Age 20 through 65 years of either sex
  • Written informed consent for study participation

Exclusion Criteria:

  • Acute rejection episode requiring specific therapy within 4 weeks before study inclusion
  • Severe impairment in general health and/or physical handicaps (malignant neoplasia, catabolic state, acute systemic infection requiring therapy)
  • Mental illness, psychiatric disorder
  • Tetracycline intolerance
  • Planned or "overt" pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00913796
Other Study ID Numbers  ICMJE 3200B0-112299
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Prof. Dr. Patrice Max Ambühl, University Hospital Zurich
Study Sponsor  ICMJE University of Zurich
Collaborators  ICMJE
  • University of Texas Southwestern Medical Center
  • Swiss Federal Institute of Technology
Investigators  ICMJE
Principal Investigator: Patrice M. Ambühl, M.D. University of Zurich
PRS Account University of Zurich
Verification Date June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP