End-stage Renal DiseasePhase 4NCT00586131
Arterial pH and Total Body Nitrogen Balances in APD
A Phase 4 study testing ammonium chloride or sodium citrate/citric acid and Sodium citrate/citratic acid in people with End-stage Renal Disease, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.
Trial summary
This study will test the hypothesis that by slightly lowering the acidity of blood (or increasing the pH), dialysis patients utilize protein and amino acids more efficiently. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- End-stage Renal Disease
- What is being tested?
- ammonium chloride or sodium citrate/citric acid and Sodium citrate/citratic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2003to Apr 2008
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women from any ethnic/racial group < 65 years.
- Treatment with CPD for 6 months and current treatment with APD for at least one month.
- Hemoglobin of at least 11.0 g/dl.
- Stable dose of erythropoietin treatment for at least the preceding three months.
- Subjects with normal nutritional status to mild malnutrition:
- Serum albumin > 3.3 g/dl
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- Relative body weight of 90-120% of the NHANES II median body weight for a given height, age range, gender and frame size.
- A normalized protein equivalent of total nitrogen appearance (nPNA) > 0.80 g/kg actual body weight/day at the time of screening.
- D/P Cr between 0.48 and 0.81 on the PET performed at the time of the screen.
- Total (renal + peritoneal) weekly Kt/V urea > 1.70 and creatinine clearance > 50 L/wk/1.73 m2.
- No evidence of primary or secondary (viz., ischemic, neuropathic) myopathy
Who cannot join
- History of active cancer other than basal cell carcinoma.
- Symptomatic severe ischemic heart disease, uncontrolled severe dysrhythmias, uncontrolled congestive heart failure, poorly controlled hypertension, severe musculoskeletal disease, arthritis or amputation of the lower extremities.
- Insulin requiring diabetes mellitus.
- Patients who received L-carnitine or anabolic hormones (other than erythropoietin) within the previous 6 months.
- Use of CaCO3 as phosphate binder.
- Severe lung or liver disease, uncontrolled asthma, active vasculitis.
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- Severe chronic infection or any other acute or chronic inflammatory or catabolic illnesses (e.g., active tuberculosis, AIDS, osteomyelitis).
- Psychosis, inability to give informed consent, evidence that patient will not comply with study protocol.
- Alcohol or other recreational drug abuse.
- Pregnancy (rare in CPD patients).
- Patients who are physically and/or psychologically incapable of undergoing the protocol.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Los Angeles Biomedical Research Institute
Torrance, California, 90502
About this study
Official title: Effect of Arterial pH on N-balances of Patients Undergoing Automated Peritoneal Dialysis
This study will test the hypothesis that by slightly lowering the acidity of blood (or increasing the pH), dialysis patients utilize protein and amino acids more efficiently.
Read the detailed description
The normal range of pH of the blood (measure of acid-base balance of body) is rather large. It is defined as a range of pH between 7.38 and 7.44. There is evidence to suggest that a high normal arterial pH (7.43-7.45) preserves nutritional status of individuals better than a low normal arterial pH (7.36-7.38). We will test this hypothesis in a small group of stable patients with end-stage renal disease undergoing automated peritoneal dialysis. It needs to be noted that all pH levels to be attained in this study are considered to be normal. The primary outcome measure for the study will be the N-balance. The changes in blood pH will be obtained by medications (ammonium chloride for lower pH and sodium bicarbonate for higher pH).
Study Procedures: A total of eight subjects with end-stage renal disease undergoing automated peritoneal dialysis will be recruited. The initial study procedures will be for purposes of screening individuals for the study. The subjects will perform 24-hour collection of urine and dialysate to assess dialysis dose and a peritoneal equilibration test to evaluate the transport properties of the peritoneum. Only those subjects who receive the minimum dialysis dose and have an average peritoneal transport type will enter the study. During this phase, the subjects will maintain a food diary to evaluate dietary preferences and dietary calorie and protein intake. These data will be used to prepare the diets for the subjects when they are admitted to the GCRC. The next two weeks will be used to evaluate the response of arterial pH to the use of the low alkali solution. If, at the end of two weeks, the arterial pH is not in the desired range, the subjects will require ammonium chloride supplementation to achieve the lower pH. In such subjects, ammonium chloride supplementation will be used for all phases of the study.
Qualifying subjects will be hospitalized in the GCRC for 41 days. The entire period of hospitalization will be divided into two equal phases of 20.5 days each: one will be the low pH phase (low alkali dialysis solution with/without ammonium chloride) and the second will be the high pH phase (high alkali dialysis solution with sodium bicarbonate with/without ammonium chloride). Nitrogen balance will be estimated during the entire period of hospitalization. N-intake is a sum of dietary and medicinal intake, while N-output will be N-losses in dialysate, urine and feces. The N-balance will be the difference between N-intake and N-output. The second outcome measure will be leucine turnover studies. Leucine turnover studies will be performed on days 21 and 41. Leucine turnover studies provide information regarding rates of total body protein synthesis and total body protein degradation as well as rates of leucine oxidation. The study will take 10 hours each - the initial 4 hours will be after an overnight fast and the last six hours will be while being fed. The third outcome measure will be the content of some proteins in a sample of muscle biopsy. Muscle biopsy will be performed on days 21 and 41 after the completion of leucine turnover studies. Finally, nutritional assessment will be performed at the time of patient admission, on day 21 and 41. On days 21 and 41, the nutritional assessment will be performed prior to the start of the leucine turnover studies.
The subjects will be compensated for participation in this study -the amount of compensation will be dependent upon the degree of participation of subjects.
Risk-benefit Assessment: The risks of the study include the risks of performing a muscle biopsy, discomfort associated with the placement of the feeding tube, emotional problems associated with prolonged hospitalization in the GCRC and risks associated with venipuncture. There are no direct benefits to the subjects as a result of their participation in this study. However, if we demonstrate that the higher arterial pH is better at preservation of nutritional status, it may have the potential of decreasing the prevalence and/or severity of protein-energy malnutrition in patients undergoing automated peritoneal dialysis.
- Conditions
- End-stage Renal Disease
- Being tested
- ammonium chloride or sodium citrate/citric acid, Sodium citrate/citratic acid
- Keywords
- end-stage renal disease, automated peritoneal dialysis, metabolic acidosis, nitrogen balances
- Medical subject headings
- Kidney Failure, Chronic, Acidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ammonium chloride or sodium citrate/citric acidDrug
Dose dictated by changes in pH
Sodium citrate/citratic acidDrug
dictated by pH
| Study group | Role | What they receive |
|---|---|---|
| Low normal pH (arterial pH 7.36-7.38) | Active comparator | Ammonium chloride or sodium citrate/citrate acid as needed to achieve the target pH Receives: Drug: ammonium chloride or sodium citrate/citric acid |
| High Normal pH (arterial pH 7.44-7.46) | Active comparator | High Normal pH (7.44-7.46) with use of increasing doses of sodium bicarbonate up until the desired pH is achieved Receives: Drug: Sodium citrate/citratic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
N-balances
Total body nitrogen balance defined as difference between nitrogen intake and nitrogen appearance in urine, stool, and dialysate
Measured: 20 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2008 (estimated)
- Study startSep 2003
- Primary completionApr 2008
- Study completionApr 2008
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 End-stage Renal DiseaseStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Treatment with sodium citrate/citric acid or ammonium chloride chloride in each phase to achieve the desired arterial pH
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rajnish Mehrotra, MD, Principal investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00586131
- Sponsor's protocol ID
- 11043
- Status last verified
- Aug 2017
- First submitted
- 21 Dec 2007
- Last updated
- 5 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mehrotra R, Bross R, Wang H, Appell M, Tso L, Kopple JD. Effect of high-normal compared with low-normal arterial pH on protein balances in automated peritoneal dialysis patients. Am J Clin Nutr. 2009 Dec;90(6):1532-40. doi: 10.3945/ajcn.2009.28285. Epub 2009 Oct 21.
PubMed 19846545
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Arterial pH on N-balances of Patients Undergoing Automated Peritoneal Dialysis
- ClinicalTrials.gov ID
- NCT00586131
- Acronym / sponsor ID
- 11043
- Conditions
- End-stage Renal Disease
- Keywords
- end-stage renal disease, automated peritoneal dialysis, metabolic acidosis, nitrogen balances
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterUniversity, hospital or other
- Study start
- Sep 2003
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 4 Jan 2008 (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.
This study will test the hypothesis that by slightly lowering the acidity of blood (or increasing the pH), dialysis patients utilize protein and amino acids more efficiently.
Detailed description
The normal range of pH of the blood (measure of acid-base balance of body) is rather large. It is defined as a range of pH between 7.38 and 7.44. There is evidence to suggest that a high normal arterial pH (7.43-7.45) preserves nutritional status of individuals better than a low normal arterial pH (7.36-7.38). We will test this hypothesis in a small group of stable patients with end-stage renal disease undergoing automated peritoneal dialysis. It needs to be noted that all pH levels to be attained in this study are considered to be normal. The primary outcome measure for the study will be the N-balance. The changes in blood pH will be obtained by medications (ammonium chloride for lower pH and sodium bicarbonate for higher pH).
Study Procedures: A total of eight subjects with end-stage renal disease undergoing automated peritoneal dialysis will be recruited. The initial study procedures will be for purposes of screening individuals for the study. The subjects will perform 24-hour collection of urine and dialysate to assess dialysis dose and a peritoneal equilibration test to evaluate the transport properties of the peritoneum. Only those subjects who receive the minimum dialysis dose and have an average peritoneal transport type will enter the study. During this phase, the subjects will maintain a food diary to evaluate dietary preferences and dietary calorie and protein intake. These data will be used to prepare the diets for the subjects when they are admitted to the GCRC. The next two weeks will be used to evaluate the response of arterial pH to the use of the low alkali solution. If, at the end of two weeks, the arterial pH is not in the desired range, the subjects will require ammonium chloride supplementation to achieve the lower pH. In such subjects, ammonium chloride supplementation will be used for all phases of the study.
Qualifying subjects will be hospitalized in the GCRC for 41 days. The entire period of hospitalization will be divided into two equal phases of 20.5 days each: one will be the low pH phase (low alkali dialysis solution with/without ammonium chloride) and the second will be the high pH phase (high alkali dialysis solution with sodium bicarbonate with/without ammonium chloride). Nitrogen balance will be estimated during the entire period of hospitalization. N-intake is a sum of dietary and medicinal intake, while N-output will be N-losses in dialysate, urine and feces. The N-balance will be the difference between N-intake and N-output. The second outcome measure will be leucine turnover studies. Leucine turnover studies will be performed on days 21 and 41. Leucine turnover studies provide information regarding rates of total body protein synthesis and total body protein degradation as well as rates of leucine oxidation. The study will take 10 hours each - the initial 4 hours will be after an overnight fast and the last six hours will be while being fed. The third outcome measure will be the content of some proteins in a sample of muscle biopsy. Muscle biopsy will be performed on days 21 and 41 after the completion of leucine turnover studies. Finally, nutritional assessment will be performed at the time of patient admission, on day 21 and 41. On days 21 and 41, the nutritional assessment will be performed prior to the start of the leucine turnover studies.
The subjects will be compensated for participation in this study -the amount of compensation will be dependent upon the degree of participation of subjects.
Risk-benefit Assessment: The risks of the study include the risks of performing a muscle biopsy, discomfort associated with the placement of the feeding tube, emotional problems associated with prolonged hospitalization in the GCRC and risks associated with venipuncture. There are no direct benefits to the subjects as a result of their participation in this study. However, if we demonstrate that the higher arterial pH is better at preservation of nutritional status, it may have the potential of decreasing the prevalence and/or severity of protein-energy malnutrition in patients undergoing automated peritoneal dialysis.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Treatment with sodium citrate/citric acid or ammonium chloride chloride in each phase to achieve the desired arterial pH
| Arm | Type | Receives |
|---|---|---|
| Low normal pH (arterial pH 7.36-7.38) | Active comparator | Drug: ammonium chloride or sodium citrate/citric acidAmmonium chloride or sodium citrate/citrate acid as needed to achieve the target pH |
| High Normal pH (arterial pH 7.44-7.46) | Active comparator | Drug: Sodium citrate/citratic acidHigh Normal pH (7.44-7.46) with use of increasing doses of sodium bicarbonate up until the desired pH is achieved |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Men and women from any ethnic/racial group < 65 years.
- Treatment with CPD for 6 months and current treatment with APD for at least one month.
- Hemoglobin of at least 11.0 g/dl.
- Stable dose of erythropoietin treatment for at least the preceding three months.
- Subjects with normal nutritional status to mild malnutrition:
Key exclusion criteria (12 listed)
- History of active cancer other than basal cell carcinoma.
- Symptomatic severe ischemic heart disease, uncontrolled severe dysrhythmias, uncontrolled congestive heart failure, poorly controlled hypertension, severe musculoskeletal disease, arthritis or amputation of the lower extremities.
- Insulin requiring diabetes mellitus.
- Patients who received L-carnitine or anabolic hormones (other than erythropoietin) within the previous 6 months.
- Use of CaCO3 as phosphate binder.
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 |
|---|---|---|
| ammonium chloride or sodium citrate/citric acidDose dictated by changes in pH | Drug | Low normal pH (arterial pH 7.36-7.38) |
| Sodium citrate/citratic aciddictated by pH | Drug | High Normal pH (arterial pH 7.44-7.46) |
Primary outcome
N-balances
Time frame: 20 days
Total body nitrogen balance defined as difference between nitrogen intake and nitrogen appearance in urine, stool, and dialysate
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 5 Sep 2017.
- Derived from this study: PubMed 19846545Mehrotra R, Bross R, Wang H, Appell M, Tso L, Kopple JD. Effect of high-normal compared with low-normal arterial pH on protein balances in automated peritoneal dialysis patients. Am J Clin Nutr. 2009 Dec;90(6):1532-40. doi: 10.3945/ajcn.2009.28285. Epub 2009 Oct 21.
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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.
Rajnish Mehrotra, MD principal investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ammonium chloride or sodium citrate/citric acid and Sodium citrate/citratic acid in people with End-stage Renal Disease, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.
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 11 inclusion and 12 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 5 Sep 2017. 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 United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
N-balances (time frame: 20 days). 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 NCT00586131, 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 5 Sep 2017.