Type 2 Diabetes Mellitus With Circulatory ComplciationNCT04390711
Association of Carbamylated HDL and CAD in T2DM Patients
An observational study of Type 2 Diabetes Mellitus With Circulatory Complciation, run by RenJi Hospital at 1 site in China.
Trial summary
This is an observational cross-sectional study aimed at investigating the alterations of the carbamylated-HDL levels in T2DM patients, and comparing the concentration of carbamylated-HDL between the T2DM patients with CAD and without CAD to explore the association between carbamylated-HDL and risk of CAD in T2DM… Read more about this study
- Who is it for?
- Ages 40 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus With Circulatory Complciation
- What is being tested?
- High density lipoprotein isolation, detection and in-vitro study.
- How many people
- 282 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2018to 30 Mar 2019
- 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 40 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Between September 2018 to March 2019, a total of 242 consecutive T2DM patients who visited Shanghai Ruijin Hospital were enrolled in this study. All patients were tested by angiography, with CAD diagnosed if luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery. Patients with end-stage renal disease (ESRD) (n = 9), acute coronary syndrome(n = 25), heart failure (n = 21), chronic viral or bacterial infection (n = 7), tumors(n = 8), or immune system disorders (n = 3) were excluded from this study. We included 40 age- and gender-matched healthy subjects to serve as the control group, who had normal blood pressure, serum fasting glucose, lipid profile, and renal function.
Who may be able to join
- 1:Clinical diagnosis of T2DM (according to the criteria of the American Diabetes Association.)
Who cannot join
- end-stage renal disease (ESRD)
- acute coronary syndrome,
- heart failure,
- chronic viral or bacterial infection,
- cancer,
- immune system disorders
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Observational Cross-sectional Study to Compare Carbamylated High-density Lipoprotein Levels Among Normal Subjects, Type 2 Diabetes Mellitus Patients With and Without Coronary Heart Disease.
This is an observational cross-sectional study aimed at investigating the alterations of the carbamylated-HDL levels in T2DM patients, and comparing the concentration of carbamylated-HDL between the T2DM patients with CAD and without CAD to explore the association between carbamylated-HDL and risk of CAD in T2DM patients.
Read the detailed description
High-density lipoprotein (HDL) is involved in various atheroprotective processes, including reverse cholesterol transport, inhibition of lipid oxidation and inflammatory cytokine secretion, endothelial repair, and antiapoptotic function, which all contribute to the regression of plague burden. Recent studies have shown that oxidative stress and chronic inflammation - both implicated in the process of diabetes - can contribute to an irreversible post-translational modification called carbamylation. Carbamylation levels reflect the burden of enhanced inflammation, oxidative stress, and renal impairment, and can serve as a biomarker of certain pathological conditions. Several clinical studies have demonstrated positive associations between cardiovascular risk, mortality, and serum carbamylation-derived product levels in the general population and particularly in patients with kidney failure. Increasing evidence also shows that carbamylated lipoprotein plays a pivotal role in atherosclerosis.18 However, most studies concerning carbamylation have been performed under a kidney disease background. Whether HDL particles in patients with type 2 diabetes mellitus (T2DM) show enhanced carbamylation and whether this enhancement is associated with vascular complications remains unknown. Thus, in the present study, the investigators aim to test whether HDL experiences carbamylation in T2DM patients and investigated the pro-atherogenic effects of carbamylated HDL on endothelial-monocyte adhesion.
- Being tested
- High density lipoprotein isolation, detection and in-vitro study.
- Keywords
- Carbamylation,HDL,T2DM
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High density lipoprotein isolation, detection and in-vitro study.Other
All blood samples were taken on the day of cardiac catheterization after overnight fasting.High density lipoprotein from each participants was isolated and further collected for carbamylation level detection and in-vitro study.
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects | We included 40 age- and gender-matched healthy subjects to serve as the control group, who had normal blood pressure, serum fasting glucose, lipid profile, and renal function. Receives: Other: High density lipoprotein isolation, detection and in-vitro study. | |
| T2DM with CAD | Diagnosis of T2DM was made according to the criteria of the American Diabetes Association. All patients were tested by angiography, with CAD diagnosed if luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery. Receives: Other: High density lipoprotein isolation, detection and in-vitro study. | |
| T2DM without CAD | Diagnosis of T2DM was made according to the criteria of the American Diabetes Association.T2DM without CAD was diagnosed if no luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery. Receives: Other: High density lipoprotein isolation, detection and in-vitro study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Carbamylated-HDL levels alteration between the control and the T2DM patients with and without concomitant CAD.
HDL was isolated from subjects' plasma and its carbamylation levels were further detected by the enzyme-linked immunosorbent assay
Measured: within 1week after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2020
- Study start1 Sep 2018
- Primary completion30 Mar 2019
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes Mellitus With Circulatory ComplciationStudies of the same condition, open and under way.
- More trials run by RenJi 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 282 participants (actual)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ruijin Hospital
- Responsible party
- Sponsor
- Investigators
- Song Ding, MD, Study director, Department of Cardiology, Ren Ji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04390711
- Sponsor's protocol ID
- c-HDL study
- Status last verified
- May 2020
- First submitted
- 8 May 2020
- Last updated
- 18 May 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rosenson RS, Brewer HB Jr, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016 Jan;13(1):48-60. doi: 10.1038/nrcardio.2015.124. Epub 2015 Sep 1.
PubMed 26323267Sun JT, Liu Y, Lu L, Liu HJ, Shen WF, Yang K, Zhang RY. Diabetes-Invoked High-Density Lipoprotein and Its Association With Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus. Am J Cardiol. 2016 Dec 1;118(11):1674-1679. doi: 10.1016/j.amjcard.2016.08.044. Epub 2016 Aug 30.
PubMed 27666175Femlak M, Gluba-Brzozka A, Cialkowska-Rysz A, Rysz J. The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 2017 Oct 30;16(1):207. doi: 10.1186/s12944-017-0594-3.
PubMed 29084567Delanghe S, Delanghe JR, Speeckaert R, Van Biesen W, Speeckaert MM. Mechanisms and consequences of carbamoylation. Nat Rev Nephrol. 2017 Sep;13(9):580-593. doi: 10.1038/nrneph.2017.103. Epub 2017 Jul 31.
PubMed 28757635Sun JT, Yang K, Mao JY, Shen WF, Lu L, Wu QH, Wang YP, Wu LP, Zhang RY. Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion. J Am Heart Assoc. 2016 Dec 16;5(12):e004700. doi: 10.1161/JAHA.116.004700.
PubMed 27986757Long J, Vela Parada X, Kalim S. Protein Carbamylation in Chronic Kidney Disease and Dialysis. Adv Clin Chem. 2018;87:37-67. doi: 10.1016/bs.acc.2018.07.002. Epub 2018 Aug 23.
PubMed 30342712Verbrugge FH, Tang WH, Hazen SL. Protein carbamylation and cardiovascular disease. Kidney Int. 2015 Sep;88(3):474-8. doi: 10.1038/ki.2015.166. Epub 2015 Jun 10.
PubMed 26061545Chen Z, Ding S, Wang YP, Chen L, Mao JY, Yang Y, Sun JT, Yang K. Association of carbamylated high-density lipoprotein with coronary artery disease in type 2 diabetes mellitus: carbamylated high-density lipoprotein of patients promotes monocyte adhesion. J Transl Med. 2020 Dec 3;18(1):460. doi: 10.1186/s12967-020-02623-2.
PubMed 33272295
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Cross-sectional Study to Compare Carbamylated High-density Lipoprotein Levels Among Normal Subjects, Type 2 Diabetes Mellitus Patients With and Without Coronary Heart Disease.
- ClinicalTrials.gov ID
- NCT04390711
- Acronym / sponsor ID
- c-HDL study
- Keywords
- Carbamylation,HDL,T2DM
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 282 participants (actual)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Collaborators
- Ruijin Hospital
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 30 Mar 2019 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 15 May 2020 (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 an observational cross-sectional study aimed at investigating the alterations of the carbamylated-HDL levels in T2DM patients, and comparing the concentration of carbamylated-HDL between the T2DM patients with CAD and without CAD to explore the association between carbamylated-HDL and risk of CAD in T2DM patients.
Detailed description
High-density lipoprotein (HDL) is involved in various atheroprotective processes, including reverse cholesterol transport, inhibition of lipid oxidation and inflammatory cytokine secretion, endothelial repair, and antiapoptotic function, which all contribute to the regression of plague burden. Recent studies have shown that oxidative stress and chronic inflammation - both implicated in the process of diabetes - can contribute to an irreversible post-translational modification called carbamylation. Carbamylation levels reflect the burden of enhanced inflammation, oxidative stress, and renal impairment, and can serve as a biomarker of certain pathological conditions. Several clinical studies have demonstrated positive associations between cardiovascular risk, mortality, and serum carbamylation-derived product levels in the general population and particularly in patients with kidney failure. Increasing evidence also shows that carbamylated lipoprotein plays a pivotal role in atherosclerosis.18 However, most studies concerning carbamylation have been performed under a kidney disease background. Whether HDL particles in patients with type 2 diabetes mellitus (T2DM) show enhanced carbamylation and whether this enhancement is associated with vascular complications remains unknown. Thus, in the present study, the investigators aim to test whether HDL experiences carbamylation in T2DM patients and investigated the pro-atherogenic effects of carbamylated HDL on endothelial-monocyte adhesion.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects | – | Other: High density lipoprotein isolation, detection and in-vitro study.We included 40 age- and gender-matched healthy subjects to serve as the control group, who had normal blood pressure, serum fasting glucose, lipid profile, and renal function. |
| T2DM with CAD | – | Other: High density lipoprotein isolation, detection and in-vitro study.Diagnosis of T2DM was made according to the criteria of the American Diabetes Association. All patients were tested by angiography, with CAD diagnosed if luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery. |
| T2DM without CAD | – | Other: High density lipoprotein isolation, detection and in-vitro study.Diagnosis of T2DM was made according to the criteria of the American Diabetes Association.T2DM without CAD was diagnosed if no luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery. |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Between September 2018 to March 2019, a total of 242 consecutive T2DM patients who visited Shanghai Ruijin Hospital were enrolled in this study. All patients were tested by angiography, with CAD diagnosed if luminal diameter narrowing was estimated visually at ≥50% in a major epicardial coronary artery. Patients with end-stage renal disease (ESRD) (n = 9), acute coronary syndrome(n = 25), heart failure (n = 21), chronic viral or bacterial infection (n = 7), tumors(n = 8), or immune system disorders (n = 3) were excluded from this study. We included 40 age- and gender-matched healthy subjects to serve as the control group, who had normal blood pressure, serum fasting glucose, lipid profile, and renal function.
Key inclusion criteria (1 listed)
- 1:Clinical diagnosis of T2DM (according to the criteria of the American Diabetes Association.)
Key exclusion criteria (6 listed)
- end-stage renal disease (ESRD)
- acute coronary syndrome,
- heart failure,
- chronic viral or bacterial infection,
- cancer,
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 |
|---|---|---|
| High density lipoprotein isolation, detection and in-vitro study.All blood samples were taken on the day of cardiac catheterization after overnight fasting.High density lipoprotein from each participants was isolated and further collected for carbamylation level detection and in-vitro study. | Other | Healthy subjects, T2DM with CAD, T2DM without CAD |
Primary outcome
Carbamylated-HDL levels alteration between the control and the T2DM patients with and without concomitant CAD.
Time frame: within 1week after enrollment
HDL was isolated from subjects' plasma and its carbamylation levels were further detected by the enzyme-linked immunosorbent assay
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 May 2020.
- Background: PubMed 26323267Rosenson RS, Brewer HB Jr, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016 Jan;13(1):48-60. doi: 10.1038/nrcardio.2015.124. Epub 2015 Sep 1.
- Background: PubMed 27666175Sun JT, Liu Y, Lu L, Liu HJ, Shen WF, Yang K, Zhang RY. Diabetes-Invoked High-Density Lipoprotein and Its Association With Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus. Am J Cardiol. 2016 Dec 1;118(11):1674-1679. doi: 10.1016/j.amjcard.2016.08.044. Epub 2016 Aug 30.
- Background: PubMed 29084567Femlak M, Gluba-Brzozka A, Cialkowska-Rysz A, Rysz J. The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 2017 Oct 30;16(1):207. doi: 10.1186/s12944-017-0594-3.
- Background: PubMed 28757635Delanghe S, Delanghe JR, Speeckaert R, Van Biesen W, Speeckaert MM. Mechanisms and consequences of carbamoylation. Nat Rev Nephrol. 2017 Sep;13(9):580-593. doi: 10.1038/nrneph.2017.103. Epub 2017 Jul 31.
- Background: PubMed 27986757Sun JT, Yang K, Mao JY, Shen WF, Lu L, Wu QH, Wang YP, Wu LP, Zhang RY. Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion. J Am Heart Assoc. 2016 Dec 16;5(12):e004700. doi: 10.1161/JAHA.116.004700.
- Background: PubMed 30342712Long J, Vela Parada X, Kalim S. Protein Carbamylation in Chronic Kidney Disease and Dialysis. Adv Clin Chem. 2018;87:37-67. doi: 10.1016/bs.acc.2018.07.002. Epub 2018 Aug 23.
- Background: PubMed 26061545Verbrugge FH, Tang WH, Hazen SL. Protein carbamylation and cardiovascular disease. Kidney Int. 2015 Sep;88(3):474-8. doi: 10.1038/ki.2015.166. Epub 2015 Jun 10.
- Derived from this study: PubMed 33272295Chen Z, Ding S, Wang YP, Chen L, Mao JY, Yang Y, Sun JT, Yang K. Association of carbamylated high-density lipoprotein with coronary artery disease in type 2 diabetes mellitus: carbamylated high-density lipoprotein of patients promotes monocyte adhesion. J Transl Med. 2020 Dec 3;18(1):460. doi: 10.1186/s12967-020-02623-2.
- Individual participant dataSharing planned: No
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.
Song Ding, MD study director
Department of Cardiology, Ren Ji Hospital
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 Type 2 Diabetes Mellitus With Circulatory Complciation, run by RenJi 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 1 inclusion and 6 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 May 2020. 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. 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?
Carbamylated-HDL levels alteration between the control and the T2DM patients with and without concomitant CAD. (time frame: within 1week after enrollment). 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 NCT04390711, which also lists 8 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 May 2020.