Peripheral Arterial DiseasesPhase 4NCT01952756
Effect of Cilostazol Endothelial Progenitor Cells and Collateral Formation in Peripheral Occlusive Artery Disease (PAOD)
A Phase 4 study testing Cilostazol in people with Peripheral Arterial Diseases, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial summary
1. The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases such as PAOD. 2. This double-blind, randomized, placebo-controlled trial to evaluate the effects of cilostazol on human early EPCs and angiogenesis as well as… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Peripheral Arterial Diseases
- What is being tested?
- Cilostazol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2012to Sep 2013
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ankle-brachial index (ABI) less than 0.9 in one or both legs but no obvious symptoms of intermittent claudication
Who cannot join
- obvious symptoms of intermittent claudication
- severe PAD (Fontaine grading > 3) or critical limb ischemia in at least one leg
- severe liver dysfunction (transaminases >10 times of upper normal limit, history of liver cirrhosis, or hepatoma)
- > stage 4 chronic kidney disease (end-stage renal disease with chronic dialysis not excluded)
- left ventricular ejection fraction <50% by echocardiography
- documented active malignancy
Show all 11Show fewer
- chronic inflammatory disease
- planned coronary intervention or endovascular therapy or bypass surgery within 3 months
- known drug allergy history for cilostazol
- current use of cilostazol or any other cAMP-elevator
- premenopausal women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells and Collateral Formation Assessed by Dual-energy 128-row CT Angiography Mediated Through Multiple Mechanisms in Patients With Mild-to-moderate PAOD
- The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases such as PAOD.
- This double-blind, randomized, placebo-controlled trial to evaluate the effects of cilostazol on human early EPCs and angiogenesis as well as the potential mechanisms of action in patients with mild-to-moderate PAOD.
Read the detailed description
- titration of drugs
- run-in period: eligible subjects are screened and baseline blood samples are obtained
- study period: 12 weeks
- 24 subjects with cilostazol and 20 subjects with dummy placebo
- On the first day after the end of the study period, the follow-up data are obtained by the same procedure
- blood sampling and measurement of serum biomarkers
- obtained from peripheral veins in all study subjects at the run-in period and the end of the treatment period of the study
- sent for isolation, cell culture, and assays of human EPCs
- also stored for enzyme-linked immunosorbent assay (Stromal cell derived factor-alfa1, adiponectin, soluble thrombomodulin, vascular endothelial growth factor)
- assays of human EPCs
- colony formation by EPCs
- quantification of EPCs and apoptotic endothelial cells
- chemotactic motility, proliferation/viability and apoptosis assays
- collateral vessels formation and distal run-off assessed by dual-energy multi-slice computed tomography angiography
- echocardiographic examinations to evaluate left ventricular functions
- Conditions
- Peripheral Arterial Diseases
- Being tested
- Cilostazol, Dummy Placebo
- Keywords
- cilostazol, endothelial progenitor cells, vasculogenesis, angiogenesis, peripheral arterial disease, biomarkers
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CilostazolDrug
Also called Pletaal (brand name)
One tablet (100 mg) twice per day for 12 weeks
Dummy PlaceboDrug
Also called Placebo, Control
One tablet twice per day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cilostazol | Active comparator | One tablet (100 mg) twice per day for 12 weeks Receives: Drug: Cilostazol |
| Dummy Placebo | Placebo comparator | One tablet twice per day for 12 weeks Receives: Drug: Dummy Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circulating EPCs Number
Peripheral blood mononuclear cells (one million cells in each) are suspended in 100 µL phosphate-buffered saline and incubated for 30 min with monoclonal antibodies against human peridinin chlorophyll protein-conjugated cluster of differentiation antigen-45, phycoerythrin-conjugated anti-human cluster of differentiation antigen-34 antibody and anti-human kinase insert domain receptor (KDR) antibody conjugated with Alexa Flour 647. Cells are washed and analyzed on a FACSCalibur flow cytometer with 100,000 events in the lymphocyte gate. EPCs, which are defined as negative for cluster of differentiation antigen-45 and positive for cluster of differentiation antigen-34 and KDR. Based on the peripheral blood mononuclear cell counts, the absolute number of circulating EPCs/µL is calculated.
Measured: 3 months
Secondary outcomes (1)
Colony Formation by EPCs
Peripheral blood mononuclear cells are isolated by density gradient centrifugation according to standard protocols. After centrifugation, cells are washed, resuspended in M199 medium supplemented with 20% (vol/vol) fetal bovine serum, 10 ng/ml vascular endothelial growth factor, 2 ng/ml basic-fibroblast growth factor, 10 ng/ml epidermal growth factor and 2 ng/ml insulin growth factor, and cultured in 24-well plates coated with human fibronectin for 7 days. EPCs cells are confirmed by uptake of acetyl-low density lipoprotein and lectin and by the expression of EPC markers. Cells are harvested after 7 days, fixed and stained with crystal violet reagent. The colony densities are quantified with an Olympus microscope at 100-fold magnification using an imaging measurement software.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2013 (estimated)
- Study startJan 2012
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseasesStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Health, Executive Yuan, R.O.C. (Taiwan)
- Responsible party
- Sponsor
- Investigators
- Ting-Hsing Chao, MD, Principal investigator, National Cheng-Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01952756
- Sponsor's protocol ID
- NCKUH-10103043/BR-100-134
- Status last verified
- Jul 2014
- First submitted
- 21 Sep 2013
- Last updated
- 18 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Chao TH, Tseng SY, Li YH, Liu PY, Cho CL, Shi GY, Wu HL, Chen JH. A novel vasculo-angiogenic effect of cilostazol mediated by cross-talk between multiple signalling pathways including the ERK/p38 MAPK signalling transduction cascade. Clin Sci (Lond). 2012 Aug 1;123(3):147-59. doi: 10.1042/CS20110432.
PubMed 22339730Biscetti F, Pecorini G, Straface G, Arena V, Stigliano E, Rutella S, Locatelli F, Angelini F, Ghirlanda G, Flex A. Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism. Int J Cardiol. 2013 Aug 10;167(3):910-6. doi: 10.1016/j.ijcard.2012.03.103. Epub 2012 Apr 2.
PubMed 22473072Chao TH, Chen IC, Li YH, Lee PT, Tseng SY. Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells. J Am Heart Assoc. 2016 May 20;5(5):e003497. doi: 10.1161/JAHA.116.003497.
PubMed 27207972
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cilostazol Enhances the Number and Functions of Circulating Endothelial Progenitor Cells and Collateral Formation Assessed by Dual-energy 128-row CT Angiography Mediated Through Multiple Mechanisms in Patients With Mild-to-moderate PAOD
- ClinicalTrials.gov ID
- NCT01952756
- Acronym / sponsor ID
- NCKUH-10103043/BR-100-134
- Conditions
- Peripheral Arterial Diseases
- Keywords
- cilostazol, endothelial progenitor cells, vasculogenesis, angiogenesis, peripheral arterial disease, biomarkers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Collaborators
- Department of Health, Executive Yuan, R.O.C. (Taiwan)
- Study start
- Jan 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 30 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.
- The number and function of circulating endothelial progenitor cells (EPCs) are inversely associated with coronary risk factors and atherosclerotic diseases such as PAOD.
- This double-blind, randomized, placebo-controlled trial to evaluate the effects of cilostazol on human early EPCs and angiogenesis as well as the potential mechanisms of action in patients with mild-to-moderate PAOD.
Detailed description
- titration of drugs
- run-in period: eligible subjects are screened and baseline blood samples are obtained
- study period: 12 weeks
- 24 subjects with cilostazol and 20 subjects with dummy placebo
- On the first day after the end of the study period, the follow-up data are obtained by the same procedure
- blood sampling and measurement of serum biomarkers
- obtained from peripheral veins in all study subjects at the run-in period and the end of the treatment period of the study
- sent for isolation, cell culture, and assays of human EPCs
- also stored for enzyme-linked immunosorbent assay (Stromal cell derived factor-alfa1, adiponectin, soluble thrombomodulin, vascular endothelial growth factor)
- assays of human EPCs
- colony formation by EPCs
- quantification of EPCs and apoptotic endothelial cells
- chemotactic motility, proliferation/viability and apoptosis assays
- collateral vessels formation and distal run-off assessed by dual-energy multi-slice computed tomography angiography
- echocardiographic examinations to evaluate left ventricular functions
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cilostazol | Active comparator | Drug: CilostazolOne tablet (100 mg) twice per day for 12 weeks |
| Dummy Placebo | Placebo comparator | Drug: Dummy PlaceboOne tablet twice per day for 12 weeks |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- ankle-brachial index (ABI) less than 0.9 in one or both legs but no obvious symptoms of intermittent claudication
Key exclusion criteria (11 listed)
- obvious symptoms of intermittent claudication
- severe PAD (Fontaine grading > 3) or critical limb ischemia in at least one leg
- severe liver dysfunction (transaminases >10 times of upper normal limit, history of liver cirrhosis, or hepatoma)
- > stage 4 chronic kidney disease (end-stage renal disease with chronic dialysis not excluded)
- left ventricular ejection fraction <50% by echocardiography
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 |
|---|---|---|
| CilostazolAlso: Pletaal (brand name)One tablet (100 mg) twice per day for 12 weeks | Drug | Cilostazol |
| Dummy PlaceboAlso: Placebo, ControlOne tablet twice per day for 12 weeks | Drug | Dummy Placebo |
Primary outcome
Circulating EPCs Number
Time frame: 3 months
Peripheral blood mononuclear cells (one million cells in each) are suspended in 100 µL phosphate-buffered saline and incubated for 30 min with monoclonal antibodies against human peridinin chlorophyll protein-conjugated cluster of differentiation antigen-45, phycoerythrin-conjugated anti-human cluster of differentiation antigen-34 antibody and anti-human kinase insert domain receptor (KDR) antibody conjugated with Alexa Flour 647. Cells are washed and analyzed on a FACSCalibur flow cytometer with 100,000 events in the lymphocyte gate. EPCs, which are defined as negative for cluster of differentiation antigen-45 and positive for cluster of differentiation antigen-34 and KDR. Based on the peripheral blood mononuclear cell counts, the absolute number of circulating EPCs/µL is calculated.
1 secondary outcome
Colony Formation by EPCs
Time frame: 3 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 18 Jul 2014.
- Background: PubMed 22339730Chao TH, Tseng SY, Li YH, Liu PY, Cho CL, Shi GY, Wu HL, Chen JH. A novel vasculo-angiogenic effect of cilostazol mediated by cross-talk between multiple signalling pathways including the ERK/p38 MAPK signalling transduction cascade. Clin Sci (Lond). 2012 Aug 1;123(3):147-59. doi: 10.1042/CS20110432.
- Background: PubMed 22473072Biscetti F, Pecorini G, Straface G, Arena V, Stigliano E, Rutella S, Locatelli F, Angelini F, Ghirlanda G, Flex A. Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism. Int J Cardiol. 2013 Aug 10;167(3):910-6. doi: 10.1016/j.ijcard.2012.03.103. Epub 2012 Apr 2.
- Derived from this study: PubMed 27207972Chao TH, Chen IC, Li YH, Lee PT, Tseng SY. Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells. J Am Heart Assoc. 2016 May 20;5(5):e003497. doi: 10.1161/JAHA.116.003497.
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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.
Ting-Hsing Chao, MD principal investigator
National Cheng-Kung University 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 Cilostazol in people with Peripheral Arterial Diseases, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
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 1 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 18 Jul 2014. 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 Taiwan. 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?
Circulating EPCs Number (time frame: 3 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 NCT01952756, which also lists 3 linked publications.
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 18 Jul 2014.