Bladder CancerPROBE-PIONCT01935466
Risk of Bladder Cancer in Type 2 Diabetes Patients With Pioglitazone Therapy "PROBE"
An observational study of Bladder Cancer, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
Pioglitazone, an agonist of the peroxisome-proliferator-activated receptor (PPAR), is a relatively new oral anti-hyperglycemic drug. Since its first approval in the USA in 1999, a potential link with bladder cancer has been a subject of debate. Read more about this study
- Who is it for?
- Ages 50 years and older, men only
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- Pioglitazone
- How many people
- 6,107 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2013to Oct 2021
- Phase
- Observational
- 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 50 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: The study group will comprise of male type 2 diabetes subjects having used pioglitazone for one year or more. The control group will include male type 2 diabetes subjects on medications other than pioglitazone adjusted for age, household income, anti-diabetic drugs, HbA1c,smoking, renal function and other bladder disorders.
Who may be able to join
- Male Type 2 diabetes subjects with age >50 year
- On anti-diabetic drugs and/or insulin for≥ 1 year
- Patient willing to provide informed consent to be included in the study
Who cannot join
- 1. Bladder cancer diagnosed before the onset of Diabetes mellitus. 2. Patient not willing to participate in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pioglitazone and Risk of Bladder Cancer in Patients With Type 2 Diabetes Mellitus"PROBE-PIO"Study
Pioglitazone, an agonist of the peroxisome-proliferator-activated receptor (PPAR), is a relatively new oral anti-hyperglycemic drug. Since its first approval in the USA in 1999, a potential link with bladder cancer has been a subject of debate. US Food and Drug Administration (FDA) in September, 2010 and European Medicines Agency in July, 2011 issued an alert about a potential relation between the occurrence of bladder cancer and the prescription of pioglitazone, based on the data from various studies. France banned its use in July 2011.
Recently Pioglitazone was banned from India without any evidence of increased bladder cancer in our population. With this background, we plan to study the risk of bladder cancer in male type 2 diabetes subjects aged more than 50 years who are on pioglitazone therapy as compared to never-users of pioglitazone in a retrospective cohort design and provide the first data from India to the policy makers regarding the purported risk in our ethnicity and geographical area.
Read the detailed description
Very recently, pioglitazone was banned for use in type 2 diabetes patients in India as well, by the notification from Government of India based on a case series - the ban was revoked a few days later due to lack of evidence.
The incidence rates of bladder cancer among different ethnicities differ markedly, with Caucasians having the highest incidence. Another important distinction pertains to the dose of pioglitazone- the daily dose of pioglitazone used in the previous studies (from western countries) was 45 mg, which is higher than currently prescribed in India (7.5-30 mg). Therefore the risk of bladder cancer in Indian patients cannot be extrapolated from studies conducted in other regions of the world. Consequently, it is an interesting issue to explore the risk of bladder cancer amongst the pioglitazone-users in our settings with different ethnicity and risk profile. There has been a single report of eight cases of sporadic bladder cancer from India.10 However, the study had no denominator and there has been no further study from India exploring the relationship between pioglitazone and bladder cancer.
Furthermore the risk of bladder cancer is highest in males greater than 50 years. The other risk factors are smoking, occupational exposure to aromatic amines in metal, leather, and paint industries etc., all of which are more common in males. The increase, if any, in the rate of bladder cancer with pioglitazone is expected to be highest in this group.
The results from currently available studies either in-vitro, animal, human (observational) on the link between pioglitazone and bladder cancer are not consistent. Whether the positive link in patients using pioglitazone in some studies could be due to the drug per se, or due to the underlying disease of diabetes, the interactions with other concomitant drugs, the inherent flaws associated with study designs and statistical analyses, or the different ethnicities between studies, are worthy of discussion. Diabetes per se may increase the risk of cancer, probably via the activation of the Ras/Raf mitogen-activated protein kinase pathway in association with a reduction of the expression of epidermal growth factor receptor. In fact, epidemiologic studies also suggest an increased risk of bladder cancer in diabetic patients, independent of the commonly used oral anti-diabetic agents or insulin.
Hence we plan to investigate the risk of bladder cancer in type 2 diabetes subjects using pioglitazone as compared to those who have never been exposed to pioglitazone. We will thoroughly scrutinize the records and also interview the subjects regarding other risk factors for bladder cancer in addition to pioglitazone.
- Conditions
- Bladder Cancer
- Being tested
- Pioglitazone
- Keywords
- Pioglitazone, Bladder cancer, Type 2 Diabetes
- Medical subject headings
- Urinary Bladder Neoplasms, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Pioglit,, Pioz
Ever users of Pioglitazone
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Ever users of Pioglitazone Receives: Drug: Pioglitazone | |
| Other drugs | Never users of pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bladder cancer rate
Kaplan-Meir survival curves will be generated for the two groups of pioglitazone users and non-pioglitazone users. All the data at the time point of interview will be considered censored. Bladder cancer rates among pioglitazone users and non-users will be compared by hazard ratio (HR) after Cox regression. Adjustment for various confounders like age, diabetes duration, region of residence, occupation, smoking, urinary tract disease, use of other medications like sulfonylurea, metformin, insulin, DPP-IV inhibitors and other cancers before baseline would be done.
Measured: Prevalent bladder cancer on pioglitazone or anti diabetic drugs for 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2013 (estimated)
- Study startJul 2013
- Primary completionOct 2021
- Study completionOct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 6,107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ashu Rastogi, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01935466
- Sponsor's protocol ID
- PROBEPIO
- Acronym
- PROBE-PIO
- Status last verified
- Jan 2022
- First submitted
- 22 Aug 2013
- Last updated
- 25 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pioglitazone and Risk of Bladder Cancer in Patients With Type 2 Diabetes Mellitus"PROBE-PIO"Study
- ClinicalTrials.gov ID
- NCT01935466
- Acronym / sponsor ID
- PROBE-PIO / PROBEPIO
- Conditions
- Bladder Cancer
- Keywords
- Pioglitazone, Bladder cancer, Type 2 Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6,107 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Oct 2021 (actual)
- Study completion
- Oct 2021 (actual)
- First posted
- 5 Sep 2013 (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.
Pioglitazone, an agonist of the peroxisome-proliferator-activated receptor (PPAR), is a relatively new oral anti-hyperglycemic drug. Since its first approval in the USA in 1999, a potential link with bladder cancer has been a subject of debate. US Food and Drug Administration (FDA) in September, 2010 and European Medicines Agency in July, 2011 issued an alert about a potential relation between the occurrence of bladder cancer and the prescription of pioglitazone, based on the data from various studies. France banned its use in July 2011.
Recently Pioglitazone was banned from India without any evidence of increased bladder cancer in our population. With this background, we plan to study the risk of bladder cancer in male type 2 diabetes subjects aged more than 50 years who are on pioglitazone therapy as compared to never-users of pioglitazone in a retrospective cohort design and provide the first data from India to the policy makers regarding the purported risk in our ethnicity and geographical area.
Detailed description
Very recently, pioglitazone was banned for use in type 2 diabetes patients in India as well, by the notification from Government of India based on a case series - the ban was revoked a few days later due to lack of evidence.
The incidence rates of bladder cancer among different ethnicities differ markedly, with Caucasians having the highest incidence. Another important distinction pertains to the dose of pioglitazone- the daily dose of pioglitazone used in the previous studies (from western countries) was 45 mg, which is higher than currently prescribed in India (7.5-30 mg). Therefore the risk of bladder cancer in Indian patients cannot be extrapolated from studies conducted in other regions of the world. Consequently, it is an interesting issue to explore the risk of bladder cancer amongst the pioglitazone-users in our settings with different ethnicity and risk profile. There has been a single report of eight cases of sporadic bladder cancer from India.10 However, the study had no denominator and there has been no further study from India exploring the relationship between pioglitazone and bladder cancer.
Furthermore the risk of bladder cancer is highest in males greater than 50 years. The other risk factors are smoking, occupational exposure to aromatic amines in metal, leather, and paint industries etc., all of which are more common in males. The increase, if any, in the rate of bladder cancer with pioglitazone is expected to be highest in this group.
The results from currently available studies either in-vitro, animal, human (observational) on the link between pioglitazone and bladder cancer are not consistent. Whether the positive link in patients using pioglitazone in some studies could be due to the drug per se, or due to the underlying disease of diabetes, the interactions with other concomitant drugs, the inherent flaws associated with study designs and statistical analyses, or the different ethnicities between studies, are worthy of discussion. Diabetes per se may increase the risk of cancer, probably via the activation of the Ras/Raf mitogen-activated protein kinase pathway in association with a reduction of the expression of epidermal growth factor receptor. In fact, epidemiologic studies also suggest an increased risk of bladder cancer in diabetic patients, independent of the commonly used oral anti-diabetic agents or insulin.
Hence we plan to investigate the risk of bladder cancer in type 2 diabetes subjects using pioglitazone as compared to those who have never been exposed to pioglitazone. We will thoroughly scrutinize the records and also interview the subjects regarding other risk factors for bladder cancer in addition to pioglitazone.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | – | Drug: PioglitazoneEver users of Pioglitazone |
| Other drugs | – | –Never users of pioglitazone |
Who may qualify
- Ages
- 50 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study group will comprise of male type 2 diabetes subjects having used pioglitazone for one year or more. The control group will include male type 2 diabetes subjects on medications other than pioglitazone adjusted for age, household income, anti-diabetic drugs, HbA1c,smoking, renal function and other bladder disorders.
Key inclusion criteria (3 listed)
- Male Type 2 diabetes subjects with age >50 year
- On anti-diabetic drugs and/or insulin for≥ 1 year
- Patient willing to provide informed consent to be included in the study
Key exclusion criteria (1 listed)
- 1. Bladder cancer diagnosed before the onset of Diabetes mellitus. 2. Patient not willing to participate in the study.
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: Pioglit,, PiozEver users of Pioglitazone | Drug | Pioglitazone |
Primary outcome
Bladder cancer rate
Time frame: Prevalent bladder cancer on pioglitazone or anti diabetic drugs for 1 year
Kaplan-Meir survival curves will be generated for the two groups of pioglitazone users and non-pioglitazone users. All the data at the time point of interview will be considered censored. Bladder cancer rates among pioglitazone users and non-users will be compared by hazard ratio (HR) after Cox regression. Adjustment for various confounders like age, diabetes duration, region of residence, occupation, smoking, urinary tract disease, use of other medications like sulfonylurea, metformin, insulin, DPP-IV inhibitors and other cancers before baseline would be done.
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 25 Jan 2022.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bladder Cancer, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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 1 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 25 Jan 2022. 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 India. 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.
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?
Bladder cancer rate (time frame: Prevalent bladder cancer on pioglitazone or anti diabetic drugs for 1 year). 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 25 Jan 2022.