Endothelial DysfunctionPhase 4NCT03639896
Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery
A Phase 4 study testing Dexmedetomidine and Saline in people with Endothelial Dysfunction and Blood Brain Barrier Defect, run by The First Affiliated Hospital of Anhui Medical University at 2 sites in China.
Trial summary
The incidence of postoperative cognitive injury is high in elderly patients, especially after major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible mechanisms that have been proposed so far include inflammation, neurotransmitter imbalance and metabolic disorders. Read more about this study
- Who is it for?
- Ages 65 to 90 years
- Conditions the study is for
- Endothelial Dysfunction, Blood Brain Barrier Defect, Postoperative Cognitive Dysfunction
- What is being tested?
- Dexmedetomidine and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 464 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jul 2019to 31 Oct 2020
- 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 65 to 90 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Written informed consent;
- Patients undergoing selective major gastrointestinal surgery with laparoscope and general anesthesia;
- Age 65-90 yrs;
- Anesthesia Society of American (ASA) Scale II~IV;
- Anticipated surgery time 2-6 hrs;
Who cannot join
- Dementia patients（Mini-mental state examination< 20）
- Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction；
- Unstable metal status and mental disease；
- A hematocrit value less than 28%in perioperative period;
- Patients with abnormal preoperative inflammatory indicators（Higher white blood cell and C-reactive protein);
- Patients undergoing cardiac and neural surgery;
- Parkinson's Disease；
- Sure or suspected abuse of analgesic and sedation drug.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Hangzhou cancer hospital
Hangzhou, Zhejiang
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui
About this study
Official title: Endothelial Injury Mechanism of Cognitive Decline and Intervention Study in Elderly Patients Undergoing Major Surgery
The incidence of postoperative cognitive injury is high in elderly patients, especially after major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible mechanisms that have been proposed so far include inflammation, neurotransmitter imbalance and metabolic disorders. In recent years, clinical studies of acute brain dysfunction after vascular endothelial injury have attracted attention.
Degradation of the endothelial glycocalyx layer and subsequent shedding of its constituents is seen as an early marker of endothelial injury, and may increase vascular permeability.Many preclinical and clinical studies have demonstrated an association between inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-10 and glycocalyx degradation biomarkers.
The scholars found evidence of plasma endothelial injury after abdominal open surgery in the elderly. Dexmedetomidine could attenuate stress response such as TNF-α, IL-1β and IL-6. Based on the above evidence, we hypothesize that elderly patients experience inflammatory response secondary to surgical traumatic stress after major surgery, greatly increasing the degree of endothelial injury (heparan sulphate and syndecan-1), reducing brain perfusion while increasing Blood-brain barrier permeability (S100B level), promoting the release of cytokines Interleukin-2(IL-2), Interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α) ,and vascular endothelial growth factor (VEGF) while reducing brain-derived neurotrophic factor(BDNF) synthesis, then leading to postoperative acute spasm. We would test the hypothesis that can reverse these effects and improve cognitive deficits.
- Being tested
- Dexmedetomidine, Saline
- Medical subject headings
- Postoperative Cognitive Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.
SalineDrug
0.5μg/kg saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | 0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over. Receives: Drug: Dexmedetomidine |
| Controlled | Placebo comparator | 0.5μg/kg Saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change of incidence of postoperative delirium
Through CAM-ICU to assess the incidence of the postoperative delirium.
Measured: The 1st, 2nd and 7th day after the surgery.
The change of incidence of postoperative cognition dysfunction
The neuropsychological tests performed at the day before the surgery, the 3rd and 7th day after the surgery respectively.Calculate the difference(ΔX) between the score obtained before surgery and 3 or 7 days after the surgery (there are both positive and negative, we use the absolute value), with this difference( ΔX) divided by the standard deviation（SD）of the difference of the normal population, that is ΔX / SD and it is the Z score.If a patient has two or more than two of the absolute value of Z scores ≥1.96, the postoperative cognition dysfunction(POCD) is exist.
Measured: 1 day Before surgery,the 3rd,7th day after the surgery.
Secondary outcomes (4)
endothelial injury levels
Plasma of patients was collected to test heparan sulphate and syndecan-1.
Measured: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Blood-brain barrier permeability
Plasma of patients was collected to test S100B level
Measured: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
The serum concentrations of BDNF
Serum level of brain-derived neurotrophic factor (BDNF) was measured.
Measured: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Inflammatory factor
Plasma of patients was collected to test cytokines IL-2, IL-6, TNF-α and VEGF level.
Measured: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2018
- Study start1 Jul 2019
- Primary completion30 Oct 2020
- Study completion31 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endothelial DysfunctionStudies 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 464 participants (actual)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Anhui Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Hangzhou Cancer Hospital
- Responsible party
- Sponsor
- Investigators
- Xinqi Cheng, PhD, Principal investigator, The First Affiliated Hospital of Anhui Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03639896
- Sponsor's protocol ID
- 7742
- Status last verified
- Sep 2019
- First submitted
- 13 Aug 2018
- Last updated
- 10 Feb 2021
- 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 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endothelial Injury Mechanism of Cognitive Decline and Intervention Study in Elderly Patients Undergoing Major Surgery
- ClinicalTrials.gov ID
- NCT03639896
- Acronym / sponsor ID
- 7742
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 464 participants (actual)
- Lead sponsor
- The First Affiliated Hospital of Anhui Medical UniversityUniversity, hospital or other
- Collaborators
- Hangzhou Cancer Hospital
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 Oct 2020 (actual)
- Study completion
- 31 Oct 2020 (actual)
- First posted
- 21 Aug 2018 (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.
The incidence of postoperative cognitive injury is high in elderly patients, especially after major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible mechanisms that have been proposed so far include inflammation, neurotransmitter imbalance and metabolic disorders. In recent years, clinical studies of acute brain dysfunction after vascular endothelial injury have attracted attention.
Degradation of the endothelial glycocalyx layer and subsequent shedding of its constituents is seen as an early marker of endothelial injury, and may increase vascular permeability.Many preclinical and clinical studies have demonstrated an association between inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-10 and glycocalyx degradation biomarkers.
The scholars found evidence of plasma endothelial injury after abdominal open surgery in the elderly. Dexmedetomidine could attenuate stress response such as TNF-α, IL-1β and IL-6. Based on the above evidence, we hypothesize that elderly patients experience inflammatory response secondary to surgical traumatic stress after major surgery, greatly increasing the degree of endothelial injury (heparan sulphate and syndecan-1), reducing brain perfusion while increasing Blood-brain barrier permeability (S100B level), promoting the release of cytokines Interleukin-2(IL-2), Interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α) ,and vascular endothelial growth factor (VEGF) while reducing brain-derived neurotrophic factor(BDNF) synthesis, then leading to postoperative acute spasm. We would test the hypothesis that can reverse these effects and improve cognitive deficits.
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 |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: Dexmedetomidine0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over. |
| Controlled | Placebo comparator | Drug: Saline0.5μg/kg Saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over. |
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- Written informed consent;
- Patients undergoing selective major gastrointestinal surgery with laparoscope and general anesthesia;
- Age 65-90 yrs;
- Anesthesia Society of American (ASA) Scale II~IV;
- Anticipated surgery time 2-6 hrs;
Key exclusion criteria (8 listed)
- Dementia patients（Mini-mental state examination< 20）
- Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction；
- Unstable metal status and mental disease；
- A hematocrit value less than 28%in perioperative period;
- Patients with abnormal preoperative inflammatory indicators（Higher white blood cell and C-reactive protein);
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 |
|---|---|---|
| Dexmedetomidine0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over. | Drug | Dexmedetomidine |
| Saline0.5μg/kg saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over. | Drug | Controlled |
Primary outcome
The change of incidence of postoperative delirium
Time frame: The 1st, 2nd and 7th day after the surgery.
Through CAM-ICU to assess the incidence of the postoperative delirium.
The change of incidence of postoperative cognition dysfunction
Time frame: 1 day Before surgery,the 3rd,7th day after the surgery.
The neuropsychological tests performed at the day before the surgery, the 3rd and 7th day after the surgery respectively.Calculate the difference(ΔX) between the score obtained before surgery and 3 or 7 days after the surgery (there are both positive and negative, we use the absolute value), with this difference( ΔX) divided by the standard deviation（SD）of the difference of the normal population, that is ΔX / SD and it is the Z score.If a patient has two or more than two of the absolute value of Z scores ≥1.96, the postoperative cognition dysfunction(POCD) is exist.
4 secondary outcomes
endothelial injury levels
Time frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Blood-brain barrier permeability
Time frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
The serum concentrations of BDNF
Time frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Inflammatory factor
Time frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
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 10 Feb 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.
Xinqi Cheng, PhD principal investigator
The First Affiliated Hospital of Anhui Medical University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine and Saline in people with Endothelial Dysfunction and Blood Brain Barrier Defect, run by The First Affiliated Hospital of Anhui Medical University at 2 sites 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 5 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 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
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?
The change of incidence of postoperative delirium (time frame: The 1st, 2nd and 7th day after the surgery.). 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 10 Feb 2021.