Stroke, IschemicNCT03334968
Prolidase Enzyme Activity in Stroke Patients
An observational study of Stroke, Ischemic and Prolidase Deficiency, run by Bezmialem Vakif University at 1 site in Turkey (Türkiye).
Trial summary
Stroke is a major cerebrovascular disease that causes significant burdens for human health and life, including high morbidity, mortality, and disability. Prolidase enzyme activity was found in various organs, such as the heart, brain, thymus, kidney, lung, pancreas, and spleen, and in plasma, leukocytes, erythrocytes… Read more about this study
- Who is it for?
- Ages 20 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke, Ischemic, Prolidase Deficiency
- How many people
- 74 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 May 2016to 1 May 2017
- 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 20 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: patients WHO were evaluated in the tertiary care clinic
Who may be able to join
- aged between 20 and 85
- admitted within 24 hours of the onset of acute ischemic stroke
Who cannot join
- patients with heart disease (such as myocardial infarction or heart failure
- chronic obstructive pulmonary disease,
- pulmonary embolism,
- pulmonary hypertension,
- tuberculosis,
- lung cancer,
- chronic renal failure,
- current hormone replacement treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Serum Prolidase Enzyme Activity as a Diagnostic Marker for Acute Ischemic Stroke
Stroke is a major cerebrovascular disease that causes significant burdens for human health and life, including high morbidity, mortality, and disability. Prolidase enzyme activity was found in various organs, such as the heart, brain, thymus, kidney, lung, pancreas, and spleen, and in plasma, leukocytes, erythrocytes, and dermal fibroblasts. An increase in collagen turnover is known to be correlated with increased prolidase enzyme activity. The aim of this study was to investigate whether SPA levels in AIS patients can be used as a potential diagnostic and prognostic marker. SPA levels were prospectively evaluated in 37 patients aged between 20 and 85 years who were admitted within 24 hours of the onset of AIS. The control group included 37 healthy volunteers of similar age without any disease.
Read the detailed description
Ischemic stroke constitutes about 80-85% of all stroke cases and is caused by the interruption of cerebral blood flow due to a blood clot. Because of reactive oxygen species (ROS) production and its oxidative metabolite activity, the brain is highly sensitive to oxidative stress. This characteristic plays an important role in the pathogenesis of ischemic and hemorrhagic brain injuries .Prolidase, which is a cytosolic exopeptidase and a member of the matrix metalloproteinase (MMP) family, cleaves iminodipeptides from carboxy-terminal ends of proline or hydroxyproline and is actively involved in collagen metabolism. It has been shown that brain MMP activity is correlated with nutritive/oxidative stress and increases during reperfusion. Furthermore, in stroke patients, elevated serum MMP levels have been reported. Biomarkers that predict the outcome and occurrence of ischemic stroke are critically important for prevention and treatment .However, serum prolidase activity (SPA) has not been previously assessed in acute ischemic stroke (AIS) patients to our knowledge. Therefore, in this study, it's aimed to investigate whether SPA levels in AIS patients can be used as a potential diagnostic and prognostic marker.In the study, 37 patients aged between 20 and 85 years who were admitted within 24 hours of the onset of AIS were prospectively evaluated. The control group consisted of 37 healthy volunteers of similar age without any disease. A comprehensive physical examination was performed consisting of a neurological examination, blood biochemistry and blood count tests, electrocardiography, and a posterior-anterior chest X-ray for all patients. AIS patients underwent transthoracic echocardiography, multi-slice computed tomography (CT), and bilateral carotid-vertebral artery Doppler ultrasonography. National Institutes of Health Stroke Scale (NIHSS) scores, measured at 24 hours, 48 hours, and 28 days after stroke, were used to determine stroke severity.Ischemic stroke subtypes classification was done according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, as cardioembolism, large-artery atherosclerosis, small artery occlusion, stroke of other determined cause, or undetermined cause. The measurement method for SPA was defined by Myara et al. The optimized method of Özcan et al. was used. Prolidase activity was evaluated with a spectrophotometric method, by measuring the proline levels. Briefly, 500 μL pre-incubation solution (50 mmol/L Tris hydrochloride buffer at power of hydrogen (pH) 7.8, with 1 mmol/L endogenous antioxidant glutathione (GSH), 5 mmol/L manganese(II) chloride (MnCl2), and 0.1% Triton X-100) and 100 μL serum were mixed; this mixture was then pre-incubated for 3 h at 37°C. A 100-μL volume of pre-incubation serum was added to 100 μL 144 mmol/L Gly-Pro solution, and this mixture was incubated for 30 min at 37°C. After the incubation, 1 ml 0.45 mol/L Trichloroacetic acid solution was added quickly to the incubation tube, and the incubation reaction was stopped. This mixture was centrifuged at 1500 rpm for 5 min, and 500 μL supernatant was removed.
- Conditions
- Stroke, Ischemic, Prolidase Deficiency
- Keywords
- Stroke, prolidase, prognosis, biomarker
- Medical subject headings
- Ischemic Stroke, Prolidase Deficiency, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patient group | Acute ischemic stroke patients | |
| Control group | Those served as control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum prolidase enzyme activity measurement
Evaluation of serum prolidase enzyme activity in stroke patients and control group
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start1 May 2016
- Primary completion1 May 2017
- Study completion1 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Stroke, IschemicStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bezmialem Vakif University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Abdulkadir Tunc, Bezmialem Vakif University
- Investigators
- Abdulkadir TUNÇ, MD, Principal investigator, Bezmialem Vakif University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03334968
- Sponsor's protocol ID
- StrokeProlidase
- Status last verified
- Nov 2017
- First submitted
- 4 Nov 2017
- Last updated
- 9 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gonullu H, Aslan M, Karadas S, Kati C, Duran L, Milanlioglu A, Aydin MN, Demir H. Serum prolidase enzyme activity and oxidative stress levels in patients with acute hemorrhagic stroke. Scand J Clin Lab Invest. 2014 Apr;74(3):199-205. doi: 10.3109/00365513.2013.873949. Epub 2014 Jan 23.
PubMed 24456419Verma AK, Raj J, Sharma V, Singh TB, Srivastava S, Srivastava R. Plasma Prolidase Activity and Oxidative Stress in Patients with Parkinson's Disease. Parkinsons Dis. 2015;2015:598028. doi: 10.1155/2015/598028. Epub 2015 Aug 9.
PubMed 26347150Tabur S, Oguz E, Eren MA, Korkmaz H, Savas E, Aksoy N, Sabuncu T. Serum prolidase activity is associated with non-diabetic metabolic syndrome. Diabetol Metab Syndr. 2014 Dec 17;6(1):142. doi: 10.1186/1758-5996-6-142. eCollection 2014.
PubMed 25540672Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH. Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2001 Dec;21(12):1393-400. doi: 10.1097/00004647-200112000-00003.
PubMed 11740200Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: application to iminodipeptiduria. Clin Chim Acta. 1982 Oct 27;125(2):193-205. doi: 10.1016/0009-8981(82)90196-6.
PubMed 7139961CHINARD FP. Photometric estimation of proline and ornithine. J Biol Chem. 1952 Nov;199(1):91-5. No abstract available.
PubMed 12999819Danton GH, Dietrich WD. Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol. 2003 Feb;62(2):127-36. doi: 10.1093/jnen/62.2.127.
PubMed 12578222
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum Prolidase Enzyme Activity as a Diagnostic Marker for Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT03334968
- Acronym / sponsor ID
- StrokeProlidase
- Conditions
- Stroke, Ischemic, Prolidase Deficiency
- Keywords
- Stroke, prolidase, prognosis, biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Bezmialem Vakif UniversityUniversity, hospital or other
- Study start
- 1 May 2016 (actual)
- Primary completion
- 1 May 2017 (actual)
- Study completion
- 1 May 2017 (actual)
- First posted
- 7 Nov 2017 (actual)
- 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.
Stroke is a major cerebrovascular disease that causes significant burdens for human health and life, including high morbidity, mortality, and disability. Prolidase enzyme activity was found in various organs, such as the heart, brain, thymus, kidney, lung, pancreas, and spleen, and in plasma, leukocytes, erythrocytes, and dermal fibroblasts. An increase in collagen turnover is known to be correlated with increased prolidase enzyme activity. The aim of this study was to investigate whether SPA levels in AIS patients can be used as a potential diagnostic and prognostic marker. SPA levels were prospectively evaluated in 37 patients aged between 20 and 85 years who were admitted within 24 hours of the onset of AIS. The control group included 37 healthy volunteers of similar age without any disease.
Detailed description
Ischemic stroke constitutes about 80-85% of all stroke cases and is caused by the interruption of cerebral blood flow due to a blood clot. Because of reactive oxygen species (ROS) production and its oxidative metabolite activity, the brain is highly sensitive to oxidative stress. This characteristic plays an important role in the pathogenesis of ischemic and hemorrhagic brain injuries .Prolidase, which is a cytosolic exopeptidase and a member of the matrix metalloproteinase (MMP) family, cleaves iminodipeptides from carboxy-terminal ends of proline or hydroxyproline and is actively involved in collagen metabolism. It has been shown that brain MMP activity is correlated with nutritive/oxidative stress and increases during reperfusion. Furthermore, in stroke patients, elevated serum MMP levels have been reported. Biomarkers that predict the outcome and occurrence of ischemic stroke are critically important for prevention and treatment .However, serum prolidase activity (SPA) has not been previously assessed in acute ischemic stroke (AIS) patients to our knowledge. Therefore, in this study, it's aimed to investigate whether SPA levels in AIS patients can be used as a potential diagnostic and prognostic marker.In the study, 37 patients aged between 20 and 85 years who were admitted within 24 hours of the onset of AIS were prospectively evaluated. The control group consisted of 37 healthy volunteers of similar age without any disease. A comprehensive physical examination was performed consisting of a neurological examination, blood biochemistry and blood count tests, electrocardiography, and a posterior-anterior chest X-ray for all patients. AIS patients underwent transthoracic echocardiography, multi-slice computed tomography (CT), and bilateral carotid-vertebral artery Doppler ultrasonography. National Institutes of Health Stroke Scale (NIHSS) scores, measured at 24 hours, 48 hours, and 28 days after stroke, were used to determine stroke severity.Ischemic stroke subtypes classification was done according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, as cardioembolism, large-artery atherosclerosis, small artery occlusion, stroke of other determined cause, or undetermined cause. The measurement method for SPA was defined by Myara et al. The optimized method of Özcan et al. was used. Prolidase activity was evaluated with a spectrophotometric method, by measuring the proline levels. Briefly, 500 μL pre-incubation solution (50 mmol/L Tris hydrochloride buffer at power of hydrogen (pH) 7.8, with 1 mmol/L endogenous antioxidant glutathione (GSH), 5 mmol/L manganese(II) chloride (MnCl2), and 0.1% Triton X-100) and 100 μL serum were mixed; this mixture was then pre-incubated for 3 h at 37°C. A 100-μL volume of pre-incubation serum was added to 100 μL 144 mmol/L Gly-Pro solution, and this mixture was incubated for 30 min at 37°C. After the incubation, 1 ml 0.45 mol/L Trichloroacetic acid solution was added quickly to the incubation tube, and the incubation reaction was stopped. This mixture was centrifuged at 1500 rpm for 5 min, and 500 μL supernatant was removed.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient group | – | –Acute ischemic stroke patients |
| Control group | – | –Those served as control group |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- patients WHO were evaluated in the tertiary care clinic
Key inclusion criteria (2 listed)
- aged between 20 and 85
- admitted within 24 hours of the onset of acute ischemic stroke
Key exclusion criteria (8 listed)
- patients with heart disease (such as myocardial infarction or heart failure
- chronic obstructive pulmonary disease,
- pulmonary embolism,
- pulmonary hypertension,
- tuberculosis,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Serum prolidase enzyme activity measurement
Time frame: 24 hours
Evaluation of serum prolidase enzyme activity in stroke patients and control group
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 9 Nov 2017.
- Results publication: PubMed 24456419Gonullu H, Aslan M, Karadas S, Kati C, Duran L, Milanlioglu A, Aydin MN, Demir H. Serum prolidase enzyme activity and oxidative stress levels in patients with acute hemorrhagic stroke. Scand J Clin Lab Invest. 2014 Apr;74(3):199-205. doi: 10.3109/00365513.2013.873949. Epub 2014 Jan 23.
- Results publication: PubMed 26347150Verma AK, Raj J, Sharma V, Singh TB, Srivastava S, Srivastava R. Plasma Prolidase Activity and Oxidative Stress in Patients with Parkinson's Disease. Parkinsons Dis. 2015;2015:598028. doi: 10.1155/2015/598028. Epub 2015 Aug 9.
- Results publication: PubMed 25540672Tabur S, Oguz E, Eren MA, Korkmaz H, Savas E, Aksoy N, Sabuncu T. Serum prolidase activity is associated with non-diabetic metabolic syndrome. Diabetol Metab Syndr. 2014 Dec 17;6(1):142. doi: 10.1186/1758-5996-6-142. eCollection 2014.
- Results publication: PubMed 11740200Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH. Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2001 Dec;21(12):1393-400. doi: 10.1097/00004647-200112000-00003.
- Results publication: PubMed 7139961Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: application to iminodipeptiduria. Clin Chim Acta. 1982 Oct 27;125(2):193-205. doi: 10.1016/0009-8981(82)90196-6.
- Results publication: PubMed 12999819CHINARD FP. Photometric estimation of proline and ornithine. J Biol Chem. 1952 Nov;199(1):91-5. No abstract available.
- Results publication: PubMed 12578222Danton GH, Dietrich WD. Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol. 2003 Feb;62(2):127-36. doi: 10.1093/jnen/62.2.127.
- Individual participant dataSharing planned: No
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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.
Abdulkadir TUNÇ, MD principal investigator
Bezmialem Vakif University
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 Stroke, Ischemic and Prolidase Deficiency, run by Bezmialem Vakif University at 1 site in Turkey (Türkiye).
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 2 inclusion and 8 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 9 Nov 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 Turkey (Türkiye). 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?
Serum prolidase enzyme activity measurement (time frame: 24 hours). 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 NCT03334968, which also lists 7 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 9 Nov 2017.