Cerebral Small Vessel DiseasesPhase 4PERFORMNCT05583266
Efficacy of Pentoxifylline on Cerebrovascular Function in Patients With Cerebral Small Vessel Disease(PERFORM)
A Phase 4 study testing Pentoxifylline sustained-release tablets in people with Cerebral Small Vessel Diseases, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
This is a randomized, double-blinded, placebo-controlled, multi-center trial. Cerebral small vessel disease (CSVD) patients will be diagnosed according to STRIVE standards and randomized into the Pentoxifylline sustained-release tablet group and placebo group. Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Cerebral Small Vessel Diseases
- What is being tested?
- Pentoxifylline sustained-release tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2022to 31 Mar 2024
- 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 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 45-75 years;
- CSVD can be seen on MRI, which satisfies one of the following conditions:
- Presence of white matter hyperintensities and Fazekas score ≥2;
- Lacunar Infarction ≥1, with or without white matter hyperintensities;
- is eligible for Transcranial Doppler (TCD) monitoring;
- meeting the following clinical manifestations:
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- Patients with vascular cognitive impairment (abnormalities in memory and or other cognitive domains lasting at least 3 months) ;
- MoCA ≤22 points; MoCA ≤21 points for primary education and below;
- independent in daily life (modified mRS ≤2) ;
- with signed informed consent.
Who cannot join
- patients with acute cerebral infarction and acute cerebral hemorrhage;
- patients with bleeding tendency: including platelet count < 100 × 10*9/L, active peptic ulcer, history of intracranial hemorrhage (such as epidural hematoma, subdural haematoma, subarachnoid hemorrhage, cerebral hemorrhage, etc.) , cerebral microbleedings (≥5 cerebral microbleedings) , brain tumor, cancer-related stroke, taking anticoagulant drugs, or using dual antiplatelet therapy;
- patients who have a history of cognitive impairment caused by other causes, such as normal pressure hydrocephalus, Alzheimer's disease, Parkinson's disease, multiple sclerosis, encephalitis, etc.;
- patients with acute coronary syndrome and severe coronary arteriosclerosis;
- patients with severe hepatic insufficiency, renal insufficiency, or severe cardiac insufficiency before randomization (severe hepatic insufficiency refers to ALT ≥2.0 times the upper limit of normal or AST ≥2.0 times the upper limit of normal; severe renal insufficiency refers to CRE ≥1.5 times the upper limit of normal or EGFR < 40 ml/min/1.73 m2; severe cardiac insufficiency refers to NYHA grade of 3-4) ;
- patients who are pregnant, lactating or likely to become pregnant and planning to become pregnant;
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- patients with refractory hypertension;
- patients with known allergic history to pentoxifylline, methylxanthine (such as caffeine, aminophylline, dihydroxypropyltheophylline, etc.) ;
- patients with use of other vasodilators or circulatory improvers within 1 week (e.g. Cilostazol, Vinpocetine, Dimitamol, Sildenafil, Butylphthalide, Betahistine, Uracillin, Alprostadil, etc.) May stop taking the drug for 1 week before enrolling if criteria are met;
- Patients using other drugs that affect the safety or efficacy evaluation of the tiral drug and who do not agree to discontinue the drug, such as GLP-1 receptor agonists, Liraglutide, dulasapeptide, risperidone, and exenatide;
- Patients with other life-threatening or serious diseases with an expected survival of < 36 months;
- Patients with contraindications to MRI;
- Patients who could not cooperate to complete the follow-up;
- Patients who enrolled in other clinical trials within 30 days.
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Tiantan Hospital
Beijing, 100050
Yilong Wang, M.D., yilong538@gmail.com
yilong wang, M.D.
About this study
Official title: Efficacy of Pentoxifylline on Cerebrovascular Function in Patients With Cerebral Small Vessel Disease(PERFORM)：A Randomized, Double-blinded, Placebo-controlled, Multi-center Trial
This is a randomized, double-blinded, placebo-controlled, multi-center trial. Cerebral small vessel disease (CSVD) patients will be diagnosed according to STRIVE standards and randomized into the Pentoxifylline sustained-release tablet group and placebo group. The purpose of this trial is to assess the efficacy of Pentoxifylline sustained- release tablets on CSVD.
Read the detailed description
Cerebral small vessel disease (CSVD) is a complex whole brain disease, which is a series of clinical, imaging, and pathological syndromes caused by various etiologies affecting small arteries, micro-arteries, capillaries, micro-venules, and small veins in the brain, and is a common clinical vascular disease of the brain, usually with insidious onset, slow progression, and some acute attacks.
The incidence of CSVD is positively correlated with age. Studies have shown that in people aged 60 to 70 years, 87% had subcortical white matter lesions and 68% had periventricular white matter changes, whereas, in people aged 80 to 90 years, 100% had subcortical white matter changes and 95% had periventricular changes. The incidence of cerebral microhemorrhage is approximately 6% in the 45-50 years old population and up to 36% in the 80-year-old population.
Pentoxifylline, a xanthine derivative, is mainly used for the improvement of cerebral circulation after ischemic cerebrovascular disease and for peripheral vascular disease, such as chronic occlusive vasculitis with intermittent claudication treatment. Pentoxifylline is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic AMP (cAMP) and activates protein kinase A31, playing an anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, and vasodilation. Pentoxifylline is a well-tolerated drug for improving peripheral blood flow disorders, primarily by increasing blood flow and increasing oxygenation of ischaemic tissues. In addition, it improves vasodilatation by increasing prostacyclin and has a specific effect on the immune response by inhibiting tumor necrosis factors.
Patients meeting the enrollment criteria will be randomly assigned to one of the two treatment groups with the use of a double-blind design (a dose of 1 tablet twice a day, from randomization to 6 months). Face-to-face interviews will be conducted at baseline, on day 30 after randomization, on day 90 after randomization, and on day 180 after randomization.
The primary endpoint was the change in cerebral blood flow (CBF) and pulsatility index of the middle cerebral artery (MCA) after 6 months of treatment based on transcranial doppler (TCD) assessment of enrolled patients. The secondary endpoints include changes in clinical symptoms, MRI imaging markers (white matter hyperintensity, lacunes, microbleeds, enlarged perivascular space), and cognitive function at 6 months. The safety endpoints include moderate or severe hemorrhage events, symptomatic and asymptomatic intracranial hemorrhage, overall mortality, and serious adverse events.
- Conditions
- Cerebral Small Vessel Diseases
- Being tested
- Pentoxifylline sustained-release tablets, Pentoxifylline sustained-release tablets placebo
- Keywords
- cerebral small vessel diseases, Pentoxifylline, randomized controlled trial, multicenter study, double blind study, placebo-controlled
- Medical subject headings
- Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pentoxifylline sustained-release tabletsDrug
a dose of 1 tablet twice a day of Pentoxifylline sustained-release tablets
Pentoxifylline sustained-release tablets placeboDrug
Pentoxifylline sustained-release tablets placebo will be administrated at the same dosage and frequency as the experimental group
| Study group | Role | What they receive |
|---|---|---|
| Pentoxifylline sustained- release tablets placebo group | Placebo comparator | This group will receive Pentoxifylline sustained-release tablets placebo, 1 tablet twice a day, from the day of randomization to 6 months. Receives: Drug: Pentoxifylline sustained-release tablets placebo |
| Pentoxifylline sustained- release tablets group | Experimental | This group will receive Pentoxifylline sustained-release tablets, 1 tablet twice a day, from the day of randomization to 6 months. Receives: Drug: Pentoxifylline sustained-release tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in cerebral blood flow at 6 months
TCD is used to evaluate the change in cerebral blood flow (cm/s) 6 months after treatment. Higher speed mean a worse outcome.
Measured: 3 months and 6 months after randomization
The change of middle cerebral artery pulsatility index at 6 months
TCD is used to evaluate the change of middle cerebral artery pulsatility index at 6 months. Higher pulsatility index mean a worse outcome.
Measured: 3 months and 6 months after randomization
Secondary outcomes (11)
cognitive function assessed by MoCA at 6 months
Cognition function assessed by Montreal Cognitive Assessment (MoCA) score. Score range 0-30. Higher scores mean a better outcome.
Measured: 6 months after randomization
cognitive function assessed by Clinical Dementia Rating (CDR) at 6 months
Cognitive function assessed by Clinical Dementia Rating (CDR). Score range 0-3. Higher scores mean a worse outcome.
Measured: 6 months after randomization
The change of White Matter hyperintense volume at 6 months
WMH volume is assessed on 3D fluid attenuated inversion recovery (FLAIR) sequence in mm3 or cm3. Larger volume indicates a worse outcome.
Measured: 6 months after randomization
The change of White Matter hyperintensities Fazekas scores at 6 months
Fazekas score is used to describe the different types of hyperintense signal abnormalities surrounding the ventricles and in the deep white matter. Periventricular hyperintensity (PVH) is graded as 0 = absence, 1 = "caps" or pencil-thin lining, 2 = smooth "halo", 3 = irregular PVH extending into the deep white matter. Separate deep white matter hyperintensity (DWMH) is rated as 0 = absence, 1 = punctate foci, 2 = beginning confluence of foci, 3 = large confluent areas. Higher scores indicats a worse outcome.
Measured: 6 months after randomization
The change of Cerebral blood flow values for MRI cerebral perfusion imaging at 6 months
MRI is used to evaluate the change of Cerebral blood flow values for MRI cerebral perfusion imaging at 6 months.
Measured: 6 months after randomization
Digit span test
The Digit span test is used to assess cognitive function change for 6 months. The score ranges from 0 to 44. Higher scores mean a better outcome.
Measured: 6 months after randomization
Stroop Color Word Test
The Stroop Color and Word Test is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. Shorter the test time, the better the outcome.
Measured: 6 months after randomization
Hamilton Anxiety Scale(HAMA)
Mood function is assessed by Hamilton Anxiety Scale(HAMA). The Score ranges 0-56. Higher scores mean a worse outcome.
Measured: 6 months after randomization
Hamilton Depression Scale(HAMD)
Mood function assessed by Hamilton Depression Scale(HAMD). The Score ranges 0-68. Higher scores mean a worse outcome.
Measured: 6 months after randomization
The Short Physical Performance Battery(SPPB)
It is a composite measure assessing walking speed, standing balance, and sit-to-stand performance. It has primarily been used to assess elderly patients both in the hospital and community setting.
Measured: 6 months after randomization
Urination and defecation
The score of the urination and defecation function scale changed at 6 months.
Measured: 6 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2022
- Study start1 Nov 2022 (estimated)
- Primary completion3 Mar 2023 (estimated)
- Study completion31 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Small Vessel DiseasesStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan 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
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, yilong Wang, Beijing Tiantan Hospital
- Investigators
- Yilong Wang, PhD，MD, Principal investigator, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05583266
- Sponsor's protocol ID
- KY2022-100-02
- Acronym
- PERFORM
- Status last verified
- Oct 2022
- First submitted
- 13 Oct 2022
- Last updated
- 17 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Pentoxifylline on Cerebrovascular Function in Patients With Cerebral Small Vessel Disease(PERFORM)：A Randomized, Double-blinded, Placebo-controlled, Multi-center Trial
- ClinicalTrials.gov ID
- NCT05583266
- Acronym / sponsor ID
- PERFORM / KY2022-100-02
- Conditions
- Cerebral Small Vessel Diseases
- Keywords
- cerebral small vessel diseases, Pentoxifylline, randomized controlled trial, multicenter study, double blind study, placebo-controlled
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Collaborators
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Study start
- 1 Nov 2022 (estimated)
- Primary completion
- 3 Mar 2023 (estimated)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 17 Oct 2022 (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.
This is a randomized, double-blinded, placebo-controlled, multi-center trial. Cerebral small vessel disease (CSVD) patients will be diagnosed according to STRIVE standards and randomized into the Pentoxifylline sustained-release tablet group and placebo group. The purpose of this trial is to assess the efficacy of Pentoxifylline sustained- release tablets on CSVD.
Detailed description
Cerebral small vessel disease (CSVD) is a complex whole brain disease, which is a series of clinical, imaging, and pathological syndromes caused by various etiologies affecting small arteries, micro-arteries, capillaries, micro-venules, and small veins in the brain, and is a common clinical vascular disease of the brain, usually with insidious onset, slow progression, and some acute attacks.
The incidence of CSVD is positively correlated with age. Studies have shown that in people aged 60 to 70 years, 87% had subcortical white matter lesions and 68% had periventricular white matter changes, whereas, in people aged 80 to 90 years, 100% had subcortical white matter changes and 95% had periventricular changes. The incidence of cerebral microhemorrhage is approximately 6% in the 45-50 years old population and up to 36% in the 80-year-old population.
Pentoxifylline, a xanthine derivative, is mainly used for the improvement of cerebral circulation after ischemic cerebrovascular disease and for peripheral vascular disease, such as chronic occlusive vasculitis with intermittent claudication treatment. Pentoxifylline is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic AMP (cAMP) and activates protein kinase A31, playing an anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, and vasodilation. Pentoxifylline is a well-tolerated drug for improving peripheral blood flow disorders, primarily by increasing blood flow and increasing oxygenation of ischaemic tissues. In addition, it improves vasodilatation by increasing prostacyclin and has a specific effect on the immune response by inhibiting tumor necrosis factors.
Patients meeting the enrollment criteria will be randomly assigned to one of the two treatment groups with the use of a double-blind design (a dose of 1 tablet twice a day, from randomization to 6 months). Face-to-face interviews will be conducted at baseline, on day 30 after randomization, on day 90 after randomization, and on day 180 after randomization.
The primary endpoint was the change in cerebral blood flow (CBF) and pulsatility index of the middle cerebral artery (MCA) after 6 months of treatment based on transcranial doppler (TCD) assessment of enrolled patients. The secondary endpoints include changes in clinical symptoms, MRI imaging markers (white matter hyperintensity, lacunes, microbleeds, enlarged perivascular space), and cognitive function at 6 months. The safety endpoints include moderate or severe hemorrhage events, symptomatic and asymptomatic intracranial hemorrhage, overall mortality, and serious adverse events.
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 |
|---|---|---|
| Pentoxifylline sustained- release tablets placebo group | Placebo comparator | Drug: Pentoxifylline sustained-release tablets placeboThis group will receive Pentoxifylline sustained-release tablets placebo, 1 tablet twice a day, from the day of randomization to 6 months. |
| Pentoxifylline sustained- release tablets group | Experimental | Drug: Pentoxifylline sustained-release tabletsThis group will receive Pentoxifylline sustained-release tablets, 1 tablet twice a day, from the day of randomization to 6 months. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 45-75 years;
- CSVD can be seen on MRI, which satisfies one of the following conditions:
- is eligible for Transcranial Doppler (TCD) monitoring;
- meeting the following clinical manifestations:
- independent in daily life (modified mRS ≤2) ;
Key exclusion criteria (14 listed)
- patients with acute cerebral infarction and acute cerebral hemorrhage;
- patients with bleeding tendency: including platelet count < 100 × 10*9/L, active peptic ulcer, history of intracranial hemorrhage (such as epidural hematoma, subdural haematoma, subarachnoid hemorrhage, cerebral hemorrhage, etc.) , cerebral microbleedings (≥5 cerebral microbleedings) , brain tumor, cancer-related stroke, taking anticoagulant drugs, or using dual antiplatelet therapy;
- patients who have a history of cognitive impairment caused by other causes, such as normal pressure hydrocephalus, Alzheimer's disease, Parkinson's disease, multiple sclerosis, encephalitis, etc.;
- patients with acute coronary syndrome and severe coronary arteriosclerosis;
- patients with severe hepatic insufficiency, renal insufficiency, or severe cardiac insufficiency before randomization (severe hepatic insufficiency refers to ALT ≥2.0 times the upper limit of normal or AST ≥2.0 times the upper limit of normal; severe renal insufficiency refers to CRE ≥1.5 times the upper limit of normal or EGFR < 40 ml/min/1.73 m2; severe cardiac insufficiency refers to NYHA grade of 3-4) ;
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 |
|---|---|---|
| Pentoxifylline sustained-release tabletsa dose of 1 tablet twice a day of Pentoxifylline sustained-release tablets | Drug | Pentoxifylline sustained- release tablets group |
| Pentoxifylline sustained-release tablets placeboPentoxifylline sustained-release tablets placebo will be administrated at the same dosage and frequency as the experimental group | Drug | Pentoxifylline sustained- release tablets placebo group |
Primary outcome
The change in cerebral blood flow at 6 months
Time frame: 3 months and 6 months after randomization
TCD is used to evaluate the change in cerebral blood flow (cm/s) 6 months after treatment. Higher speed mean a worse outcome.
The change of middle cerebral artery pulsatility index at 6 months
Time frame: 3 months and 6 months after randomization
TCD is used to evaluate the change of middle cerebral artery pulsatility index at 6 months. Higher pulsatility index mean a worse outcome.
11 secondary outcomes
cognitive function assessed by MoCA at 6 months
Time frame: 6 months after randomization
cognitive function assessed by Clinical Dementia Rating (CDR) at 6 months
Time frame: 6 months after randomization
The change of White Matter hyperintense volume at 6 months
Time frame: 6 months after randomization
The change of White Matter hyperintensities Fazekas scores at 6 months
Time frame: 6 months after randomization
The change of Cerebral blood flow values for MRI cerebral perfusion imaging at 6 months
Time frame: 6 months after randomization
Digit span test
Time frame: 6 months after randomization
Stroop Color Word Test
Time frame: 6 months after randomization
Hamilton Anxiety Scale(HAMA)
Time frame: 6 months after randomization
Hamilton Depression Scale(HAMD)
Time frame: 6 months after randomization
The Short Physical Performance Battery(SPPB)
Time frame: 6 months after randomization
Urination and defecation
Time frame: 6 months after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 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.
Yilong Wang, PhD，MD principal investigator
Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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 Pentoxifylline sustained-release tablets in people with Cerebral Small Vessel Diseases, run by Beijing Tiantan Hospital at 1 site in China.
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 10 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 17 Oct 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yilong Wang, PhD，MD (0086-10-59975178, yilong528@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change in cerebral blood flow at 6 months (time frame: 3 months and 6 months after randomization). 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 17 Oct 2022.