End-stage Renal DiseasePhase 4PPARNCT00745225
Peroxisome Proliferator-Activated Receptor-Gamma Activation in Peritoneal Dialysis Patients
A Phase 4 study testing Pioglitazone in people with End-stage Renal Disease, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
To study whether peroxisome proliferator-activated receptor-gamma activation in peritoneal dialysis patients will reduce inflammation, atherosclerosis, calcification and improve survival of peritoneal dialysis patients Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- End-stage Renal Disease
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteHong Kong
- Study dates
- Feb 2006to Dec 2014
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Both prevalent patients or patients newly started on continuous peritoneal dialysis, with or without diabetes mellitus will be considered eligible for study entry.
- For patients newly started on chronic peritoneal dialysis, they will be suitable for recruitment into the study after one month on peritoneal dialysis.
- Patients who provide informed consent for the study
Who cannot join
- Patients with underlying active malignancy
- Patients with chronic liver disease or liver cirrhosis
- Patients with active infections
- Patients with other chronic active inflammatory disease such as systemic lupus erythematosus, rheumatoid arthritis
- Patients who refuse study participation
- Patients with underlying congenital heart disease or rheumatic heart disease
Show all 12Show fewer
- Patients with poor general condition
- Patients with plans for living related kidney transplant within 2 years
- Female patients with pregnancy
- Patients with history of recurrent hypoglycemia
- Patients with Class III and IV congestive heart failure
- Patients already receiving glitazones treatment at the screening visit
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Targeting Peroxisome Proliferator-Activated Receptor-Gamma in Peritoneal Dialysis Patients - Will it Reduce Inflammation, Atherosclerosis, Calcification and Improve Survival of Peritoneal Dialysis Patients? (PROOF Trial)
To study whether peroxisome proliferator-activated receptor-gamma activation in peritoneal dialysis patients will reduce inflammation, atherosclerosis, calcification and improve survival of peritoneal dialysis patients
Read the detailed description
Peritoneal dialysis patients are at increased risk of cardiovascular morbidity and mortality and are related to the presence of accelerated atherosclerosis. Other than the traditional cardiovascular risk factors, there is increasing evidence that inflammation is associated with the development of atherosclerosis and cardiovascular events in both the general and dialysis population. C-reactive protein is predictive of higher all-cause mortality and cardiovascular mortality, independent of other cardiovascular risk factors and atherosclerotic vascular disease. As a considerable proportion of peritoneal dialysis patients showed elevated C-reactive protein, it raises an important question as to whether lowering C-reactive protein will have any cardiovascular and survival benefit in these patients. On the other hand, insulin resistance with associated hyperinsulinemia is frequently observed in chronic renal failure and dialysis patients. Although the exact mechanism of insulin resistance needs further evaluation, studies indicated that insulin resistance is an important cardiovascular risk factor and outcome predictor in the general and dialysis population. Moreover, recent evidence indicates an association between chronic inflammation and insulin resistance although the exact interrelationship remains unclear. The peroxisome proliferator-activated receptor-gamma (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. PPAR-g is highly expressed in adipose tissue and clinical study has confirmed efficacy of the specific ligands for PPAR-gamma, namely thiazolidinediones (TZD), in improving insulin sensitivity. Recent experimental and clinical studies demonstrated that TZD has anti-inflammatory and anti-atherosclerotic properties other than insulin sensitizing effect in type 2 diabetics. We hypothesize that modulation of the PPAR-g activity may be a novel therapeutic strategy for reducing inflammation and improving insulin sensitivity and may retard the progression of atherosclerosis and possibly reduce mortality of our peritoneal dialysis patients.
- Conditions
- End-stage Renal Disease
- Being tested
- Pioglitazone, placebo comparator
- Keywords
- peritoneal dialysis, cardiovascular, PPAR-gamma
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
pioglitazone 15mg daily for 12 weeks, then 30mg daily for 84 weeks
placebo comparatorDrug
Also called Placebo
1 capsule daily, 96 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Active intervention arm | Experimental | Peroxisome proliferator activator receptor gamma treatment, Pioglitazone Receives: Drug: Pioglitazone |
| placebo pill | Placebo comparator | placebo comparator Receives: Drug: placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in carotid intima-media thickness
Change in carotid intima-media thickness
Measured: over 48 weeks
change in flow mediated dilatation (marker of endothelial function)
change in flow mediated dilatation (marker of endothelial function)
Measured: over 48 weeks
Secondary outcomes (21)
change in aortic pulse wave velocity
change in aortic pulse wave velocity
Measured: over 96 weeks
change in augmentation index-heart rate adjusted
change in augmentation index-heart rate adjusted
Measured: over 96 weeks
change in nitroglycerin-mediated dilatation
change in nitroglycerin-mediated dilatation
Measured: over 48 weeks
change in coronary artery calcium score
change in coronary artery calcium score
Measured: over 96 weeks
change in heart valves calcium score
change in heart valves calcium score
Measured: over 96 weeks
change in carotid artery calcium score
change in carotid artery calcium score
Measured: over 96 weeks
change in abdominal visceral fat
change in abdominal visceral fat
Measured: over 96 weeks
change in subcutaneous fat
change in subcutaneous fat
Measured: over 96 weeks
change in blood pressure
change in blood pressure
Measured: over 96 weeks
change in C-reactive protein
change in C-reactive protein
Measured: over 96 weeks
change in residual kidney function
change in residual kidney function
Measured: over 96 weeks
change in HOMA index (among those not on insulin)
Change in insulin resistance index
Measured: over 96 weeks
change in D/P creatinine ratio
Change in peritoneal solute transport parameter
Measured: over 96 weeks
change in peritoneal ultrafiltration with 2.5% during PET
Change in peritoneal ultrafiltration volume
Measured: over 96 weeks
change in handgrip strength
change in handgrip strength
Measured: over 96 weeks
Change in cardiac biomarkers
change in cardiac biomarkers
Measured: over 96 weeks
change in insulin dose (among those on insulin)
change in insulin dose
Measured: over 96 weeks
change in endothelial progenitor cells
change in endothelial progenitor cells
Measured: over 96 weeks
change in central systolic blood pressure
change in central systolic blood pressure
Measured: over 96 weeks
Change in central diastolic blood pressure
change in central diastolic blood pressure
Measured: over 96 weeks
change in glycemic control (fasting glucose, and glycosylated hemoglobin)
change in glycemic control
Measured: over 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2008 (estimated)
- Study startFeb 2006
- Primary completionOct 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End-stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind randomized placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Responsible party
- Principal investigator, Dr. Angela Yee-Moon Wang, The University of Hong Kong
- Investigators
- Angela YM Wang, MD, PhD, FRCP, Principal investigator, University of Hong Kong, Queen Mary Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00745225
- Sponsor's protocol ID
- A111-101
- Acronym
- PPAR
- Status last verified
- Oct 2021
- First submitted
- 1 Sep 2008
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Peroxisome Proliferator-Activated Receptor-Gamma in Peritoneal Dialysis Patients - Will it Reduce Inflammation, Atherosclerosis, Calcification and Improve Survival of Peritoneal Dialysis Patients? (PROOF Trial)
- ClinicalTrials.gov ID
- NCT00745225
- Acronym / sponsor ID
- PPAR / A111-101
- Conditions
- End-stage Renal Disease
- Keywords
- peritoneal dialysis, cardiovascular, PPAR-gamma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Study start
- Feb 2006 (actual)
- Primary completion
- Oct 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 3 Sep 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.
To study whether peroxisome proliferator-activated receptor-gamma activation in peritoneal dialysis patients will reduce inflammation, atherosclerosis, calcification and improve survival of peritoneal dialysis patients
Detailed description
Peritoneal dialysis patients are at increased risk of cardiovascular morbidity and mortality and are related to the presence of accelerated atherosclerosis. Other than the traditional cardiovascular risk factors, there is increasing evidence that inflammation is associated with the development of atherosclerosis and cardiovascular events in both the general and dialysis population. C-reactive protein is predictive of higher all-cause mortality and cardiovascular mortality, independent of other cardiovascular risk factors and atherosclerotic vascular disease. As a considerable proportion of peritoneal dialysis patients showed elevated C-reactive protein, it raises an important question as to whether lowering C-reactive protein will have any cardiovascular and survival benefit in these patients. On the other hand, insulin resistance with associated hyperinsulinemia is frequently observed in chronic renal failure and dialysis patients. Although the exact mechanism of insulin resistance needs further evaluation, studies indicated that insulin resistance is an important cardiovascular risk factor and outcome predictor in the general and dialysis population. Moreover, recent evidence indicates an association between chronic inflammation and insulin resistance although the exact interrelationship remains unclear. The peroxisome proliferator-activated receptor-gamma (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. PPAR-g is highly expressed in adipose tissue and clinical study has confirmed efficacy of the specific ligands for PPAR-gamma, namely thiazolidinediones (TZD), in improving insulin sensitivity. Recent experimental and clinical studies demonstrated that TZD has anti-inflammatory and anti-atherosclerotic properties other than insulin sensitizing effect in type 2 diabetics. We hypothesize that modulation of the PPAR-g activity may be a novel therapeutic strategy for reducing inflammation and improving insulin sensitivity and may retard the progression of atherosclerosis and possibly reduce mortality of our peritoneal dialysis patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind randomized placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Active intervention arm | Experimental | Drug: PioglitazonePeroxisome proliferator activator receptor gamma treatment, Pioglitazone |
| placebo pill | Placebo comparator | Drug: placebo comparatorplacebo comparator |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Both prevalent patients or patients newly started on continuous peritoneal dialysis, with or without diabetes mellitus will be considered eligible for study entry.
- For patients newly started on chronic peritoneal dialysis, they will be suitable for recruitment into the study after one month on peritoneal dialysis.
- Patients who provide informed consent for the study
Key exclusion criteria (12 listed)
- Patients with underlying active malignancy
- Patients with chronic liver disease or liver cirrhosis
- Patients with active infections
- Patients with other chronic active inflammatory disease such as systemic lupus erythematosus, rheumatoid arthritis
- Patients who refuse study participation
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 |
|---|---|---|
| PioglitazoneAlso: Actospioglitazone 15mg daily for 12 weeks, then 30mg daily for 84 weeks | Drug | Active intervention arm |
| placebo comparatorAlso: Placebo1 capsule daily, 96 weeks. | Drug | placebo pill |
Primary outcome
Change in carotid intima-media thickness
Time frame: over 48 weeks
Change in carotid intima-media thickness
change in flow mediated dilatation (marker of endothelial function)
Time frame: over 48 weeks
change in flow mediated dilatation (marker of endothelial function)
21 secondary outcomes
change in aortic pulse wave velocity
Time frame: over 96 weeks
change in augmentation index-heart rate adjusted
Time frame: over 96 weeks
change in nitroglycerin-mediated dilatation
Time frame: over 48 weeks
change in coronary artery calcium score
Time frame: over 96 weeks
change in heart valves calcium score
Time frame: over 96 weeks
change in carotid artery calcium score
Time frame: over 96 weeks
change in abdominal visceral fat
Time frame: over 96 weeks
change in subcutaneous fat
Time frame: over 96 weeks
change in blood pressure
Time frame: over 96 weeks
change in C-reactive protein
Time frame: over 96 weeks
change in residual kidney function
Time frame: over 96 weeks
change in HOMA index (among those not on insulin)
Time frame: over 96 weeks
change in D/P creatinine ratio
Time frame: over 96 weeks
change in peritoneal ultrafiltration with 2.5% during PET
Time frame: over 96 weeks
change in handgrip strength
Time frame: over 96 weeks
Change in cardiac biomarkers
Time frame: over 96 weeks
change in insulin dose (among those on insulin)
Time frame: over 96 weeks
change in endothelial progenitor cells
Time frame: over 96 weeks
change in central systolic blood pressure
Time frame: over 96 weeks
Change in central diastolic blood pressure
Time frame: over 96 weeks
change in glycemic control (fasting glucose, and glycosylated hemoglobin)
Time frame: over 96 weeks
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 8 Oct 2021.
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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.
Angela YM Wang, MD, PhD, FRCP principal investigator
University of Hong Kong, Queen Mary Hospital
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 Pioglitazone in people with End-stage Renal Disease, run by The University of Hong Kong at 1 site in Hong Kong.
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 3 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 8 Oct 2021. 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 Hong Kong. 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. Some participants in this study may receive a placebo. 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?
Change in carotid intima-media thickness (time frame: over 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2021.