HematuriaEarly Phase 1NCT01738815
Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer
A Early Phase 1 study testing Valproic Acid in people with Hematuria and Bladder Cancer, run by State University of New York - Upstate Medical University at 1 site in United States.
Trial summary
The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Hematuria, Bladder Cancer
- What is being tested?
- Valproic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Apr 2014
- Phase
- Early Phase 1
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient over the age of 21
- Bladder tumor suspected or confirmed
- ECOG status 0 to 2
- Premedication Lab values:
- Absolute Neutrophil Count >750 cells/m3 AST/ALT less than 1.5xN Amylase less than 1.5xN Platelet Count > 125,000 PT/PTT > 1.3xN Hemoglobin > 8gm/dL Creatinine less than 1.5xN
Who cannot join
- Allergy to valproic acid
- Concurrent chemotherapy
- Pre-menopausal women
- Active systemic infection (HepatitisB,C)
- Coagulation disorders
- Concurrent medication: Tolbutamide, Warfarin, Zidovudine, Benzodiazepine, Clonazepam, Diazepam, Any anti-convulsant therapy
Show all 11Show fewer
- Seizure disorder
- Dementia
- History of Pancreatitis
- HIV diagnosis/treatment
- Liver disease/dysfunction
Trial locations and contacts
1 site in 1 country.
United States1 site
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth.
Read the detailed description
Bladder cancer is the fourth most common cancer in the United States with over 60,000 new cases each year. It can usually be treated initially by insertion of an endoscope into the bladder and surgically removing the tumor, a procedure known as cystoscopy and trans-urethral resection of bladder tumor (TURBT). For most patients this procedure will successfully remove all of the detectable tumor. Unfortunately over 40% of all patients will develop a cancer recurrence in less than two years and all patients remain at increased risk of recurrence for the remainder of their lives. This risk requires life long monitoring and this is best accomplished with regular cystoscopic examinations. The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth. Patients with suspected bladder cancer will be invited to participate in the study, if a tumor is observed during cystoscopy it will be sampled for research purposes and then according to standards of care, the patient scheduled for TURBT under general anesthesia. In the interval between discovery of a bladder tumor and resection, usually two to four weeks, the patient will be given valproic acid to take orally. In addition, tumors from patients with known or suspected bladder cancer referred for TURBT or cystectomy will be sampled. The tumor pieces obtained before and after taking valproic acid and from the referral patients not treated with valproic acid will be analyzed to see if the drug has changed what genes are active. We have found that valproic acid causes bladder cancer cells to make more of the protein, thrombospondin-1. This protein inhibits the growth of new blood vessels and so increased thrombospondin-1 in bladder tumors should inhibit their growth by decreasing the blood supply. Valproic acid may change thrombospondin-1 levels through inhibition of histone deacetylases. We will also assay HDAC activity in the tumor specimens. If valproic acid alters thrombospondin-1 levels and HDAC activity in bladder cancer patients further study to see if it can reduce growth will be justified. Valproic acid is a drug approved for the treatment of seizure disorders that is generally well tolerated with few side effects. It may prove useful in reducing bladder cancer recurrence and progression.
- Conditions
- Hematuria, Bladder Cancer
- Being tested
- Valproic Acid
- Keywords
- bladder cancer, hematuria, sodium valproate, valproic acid
- Medical subject headings
- Hematuria, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
Also called Depakote ER
500 mg orally, once daily for up to 30 days
| Study group | Role | What they receive |
|---|---|---|
| valproic acid | Experimental | Patients will be administered valproic acid (Depakote ER) for up to 30 days prior to tumor resection Receives: Drug: Valproic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thrombospondin-1 gene expression
Expression of thrombospondin-1 will be assayed using quantitative real-time PCR and western blotting. Comparisons will be intra-patient for paired specimens acquired prior to and after treatment and inter-patient for treated and un-treated patients.
Measured: 1 day
Secondary outcomes (1)
Angiogenesis, proliferation, and histone deacetylase activity markers
Histone deacetylase activity, angiogenesis, and proliferation markers will be assayed using qPCR and western blotting of tumor biopsy specimens. Comparisons will be intra-patient for paired specimens acquired prior to and after treatment and inter-patient for treated and un-treated patients.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2012 (estimated)
- Study startDec 2011
- Primary completionMay 2013
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HematuriaStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York - Upstate Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Oleg Shapiro, MD, Principal investigator, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01738815
- Sponsor's protocol ID
- 256549
- Status last verified
- Oct 2021
- First submitted
- 28 Nov 2012
- Last updated
- 22 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer
- ClinicalTrials.gov ID
- NCT01738815
- Acronym / sponsor ID
- 256549
- Conditions
- Hematuria, Bladder Cancer
- Keywords
- bladder cancer, hematuria, sodium valproate, valproic acid
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- State University of New York - Upstate Medical UniversityUniversity, hospital or other
- Study start
- Dec 2011 (actual)
- Primary completion
- May 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 30 Nov 2012 (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.
The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth.
Detailed description
Bladder cancer is the fourth most common cancer in the United States with over 60,000 new cases each year. It can usually be treated initially by insertion of an endoscope into the bladder and surgically removing the tumor, a procedure known as cystoscopy and trans-urethral resection of bladder tumor (TURBT). For most patients this procedure will successfully remove all of the detectable tumor. Unfortunately over 40% of all patients will develop a cancer recurrence in less than two years and all patients remain at increased risk of recurrence for the remainder of their lives. This risk requires life long monitoring and this is best accomplished with regular cystoscopic examinations. The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth. Patients with suspected bladder cancer will be invited to participate in the study, if a tumor is observed during cystoscopy it will be sampled for research purposes and then according to standards of care, the patient scheduled for TURBT under general anesthesia. In the interval between discovery of a bladder tumor and resection, usually two to four weeks, the patient will be given valproic acid to take orally. In addition, tumors from patients with known or suspected bladder cancer referred for TURBT or cystectomy will be sampled. The tumor pieces obtained before and after taking valproic acid and from the referral patients not treated with valproic acid will be analyzed to see if the drug has changed what genes are active. We have found that valproic acid causes bladder cancer cells to make more of the protein, thrombospondin-1. This protein inhibits the growth of new blood vessels and so increased thrombospondin-1 in bladder tumors should inhibit their growth by decreasing the blood supply. Valproic acid may change thrombospondin-1 levels through inhibition of histone deacetylases. We will also assay HDAC activity in the tumor specimens. If valproic acid alters thrombospondin-1 levels and HDAC activity in bladder cancer patients further study to see if it can reduce growth will be justified. Valproic acid is a drug approved for the treatment of seizure disorders that is generally well tolerated with few side effects. It may prove useful in reducing bladder cancer recurrence and progression.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| valproic acid | Experimental | Drug: Valproic AcidPatients will be administered valproic acid (Depakote ER) for up to 30 days prior to tumor resection |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patient over the age of 21
- Bladder tumor suspected or confirmed
- ECOG status 0 to 2
- Premedication Lab values:
- Absolute Neutrophil Count >750 cells/m3 AST/ALT less than 1.5xN Amylase less than 1.5xN Platelet Count > 125,000 PT/PTT > 1.3xN Hemoglobin > 8gm/dL Creatinine less than 1.5xN
Key exclusion criteria (11 listed)
- Allergy to valproic acid
- Concurrent chemotherapy
- Pre-menopausal women
- Active systemic infection (HepatitisB,C)
- Coagulation disorders
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 |
|---|---|---|
| Valproic AcidAlso: Depakote ER500 mg orally, once daily for up to 30 days | Drug | valproic acid |
Primary outcome
Thrombospondin-1 gene expression
Time frame: 1 day
Expression of thrombospondin-1 will be assayed using quantitative real-time PCR and western blotting. Comparisons will be intra-patient for paired specimens acquired prior to and after treatment and inter-patient for treated and un-treated patients.
1 secondary outcome
Angiogenesis, proliferation, and histone deacetylase activity markers
Time frame: 1 day
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 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.
Oleg Shapiro, MD principal investigator
State University of New York - Upstate Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Valproic Acid in people with Hematuria and Bladder Cancer, run by State University of New York - Upstate Medical University 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 5 inclusion and 11 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 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 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Thrombospondin-1 gene expression (time frame: 1 day). 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 22 Oct 2021.