Renal Transplant PatientsPhase 2MARTNCT00913796
Metabolic Acidosis in Renal Transplant Patients
A Phase 2 study testing Potassium citrate and Potassium chloride in people with Renal Transplant Patients and Metabolic Acidosis, run by University of Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Renal Transplant Patients, Metabolic Acidosis, Physical Capacity
- What is being tested?
- Potassium citrate and Potassium chloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2007to Mar 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital of Zurich
Zurich, Canton of Zurich, CH 8091
About this study
Official title: Metabolic Acidosis and Its Impact on Mineral Metabolism and Physical Performance in Renal Transplant Patients
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
- to determine the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis
- to study the effect of substituting base equivalents (citrate) on acid/base status of renal transplant patients with acidosis
- to compare the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis before and after substitution with citrate
Read the 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.
- Conditions
- Renal Transplant Patients, Metabolic Acidosis, Physical Capacity, Bone Disease, Mineral Metabolism
- Being tested
- Potassium citrate, Potassium chloride
- Keywords
- Renal transplantation, Metabolic acidosis, Physical capacity, Bone histology, Bone histomorphometry, Parathyroid function, Calcium and phosphate metabolism
- Medical subject headings
- Acidosis, Bone Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium citrateDrug
2.41 gram of citrate b.i.d. for 12 months. Dosage to be adjusted according to serum potassium concentration.
Potassium chlorideDrug
370 mg potassium t.i.d. for 12 months. Dosage to be adjusted according to serum postassium concentration.
| Study group | Role | What they receive |
|---|---|---|
| Postassium citrate | Experimental | Aim: correction of metabolic acidosis Receives: Drug: Potassium citrate |
| Potassium chloride | Active comparator | Potassium chloride is given to compensate for any possible effects of potassium in potassium citrate (primary treatment). Receives: Drug: Potassium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correction of metabolic acidosis
Measured: 12 months
Secondary outcomes (1)
Improvement in physical capacity
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2009 (estimated)
- Study startDec 2007
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Transplant PatientsStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas Southwestern Medical Center, Swiss Federal Institute of Technology
- Investigators
- Patrice M. Ambühl, M.D., Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00913796
- Sponsor's protocol ID
- 3200B0-112299
- Acronym
- MART
- Status last verified
- Jun 2009
- First submitted
- 1 Apr 2009
- Last updated
- 22 Oct 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Starke A, Corsenca A, Kohler T, Knubben J, Kraenzlin M, Uebelhart D, Wuthrich RP, von Rechenberg B, Muller R, Ambuhl 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. doi: 10.2215/CJN.01100112. Epub 2012 Jul 5.
PubMed 22773591
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Acidosis and Its Impact on Mineral Metabolism and Physical Performance in Renal Transplant Patients
- ClinicalTrials.gov ID
- NCT00913796
- Acronym / sponsor ID
- MART / 3200B0-112299
- Conditions
- Renal Transplant Patients, Metabolic Acidosis, Physical Capacity, Bone Disease, Mineral Metabolism
- Keywords
- Renal transplantation, Metabolic acidosis, Physical capacity, Bone histology, Bone histomorphometry, Parathyroid function, Calcium and phosphate metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- University of Texas Southwestern Medical Center, Swiss Federal Institute of Technology
- Study start
- Dec 2007
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 4 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- to determine the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis
- to study the effect of substituting base equivalents (citrate) on acid/base status of renal transplant patients with acidosis
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Postassium citrate | Experimental | Drug: Potassium citrateAim: correction of metabolic acidosis |
| Potassium chloride | Active comparator | Drug: Potassium chloridePotassium chloride is given to compensate for any possible effects of potassium in potassium citrate (primary treatment). |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| Potassium citrate2.41 gram of citrate b.i.d. for 12 months. Dosage to be adjusted according to serum potassium concentration. | Drug | Postassium citrate |
| Potassium chloride370 mg potassium t.i.d. for 12 months. Dosage to be adjusted according to serum postassium concentration. | Drug | Potassium chloride |
Primary outcome
Correction of metabolic acidosis
Time frame: 12 months
1 secondary outcome
Improvement in physical capacity
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2010.
- Derived from this study: PubMed 22773591Starke A, Corsenca A, Kohler T, Knubben J, Kraenzlin M, Uebelhart D, Wuthrich RP, von Rechenberg B, Muller R, Ambuhl 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. doi: 10.2215/CJN.01100112. Epub 2012 Jul 5.
Related trials for Renal Transplant Patients
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingObservational study
Cardiovascular Risk Assessment For Kidney Transplantation - Utility of Computed Tomography Coronary Angiography in the Assessment of Patients Awaiting Kidney Transplantation
Cardiovascular Diseases, Kidney Transplant; Complications
Recruiting
Multidisciplinary Non-Pharmacological Intervention to Improve Quality of Life in Solid Organ Transplant Recipients
Heart Transplant Patients, Kidney Transplant Patients
RecruitingPhase 1/2
Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders
Autoimmune Disorders, Systemic Sclerosis
Active, not recruiting
Leveraging Technology to Improve Medication Adherence in Youth With Kidney or Liver Transplant
Transplant;Failure,Kidney, Transplant; Failure, Liver
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.
Patrice M. Ambühl, M.D. principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Potassium citrate and Potassium chloride in people with Renal Transplant Patients and Metabolic Acidosis, run by University of Zurich at 1 site in Switzerland.
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 6 inclusion and 5 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 22 Oct 2010. 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 Switzerland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Correction of metabolic acidosis (time frame: 12 months). 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 NCT00913796, which also lists 1 linked publication.
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 22 Oct 2010.