Peripheral Arterial DiseaserhsppvldaNCT04787770
The Role of HSP90 in Peripheral Vascular Lesions of Diabetic Atherosclerosis
An observational study of Peripheral Arterial Disease, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial summary
Diabetic foot disease with a global incidence of about 6% is one of the most serious complications of diabetes, which brings great pain and economic burden to patients.In China, the incidence rate is 8.1%, and the amputation rate is 7.3%. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- non-intervention
- How many people
- 150 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2020to 10 Dec 2020
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 150 cases, 50 cases in each group.
Who may be able to join
- Diagnostic criteria for diabetes: using WHO1999 diabetes diagnostic criteria, that is, (1) having diabetes symptoms (polyuria, polydipsia, and unexplained weight loss), and random (any time after meal) plasma glucose ≥11.1mmol/L(200mg/ dL);(2), or fasting (fasting for at least 8 hours) plasma glucose ≥7.0mmol/L(126mg/ dL);(3), or OGTT 2 hours plasma glucose ≥11.1mmol/L(200mg/ dL)
- Inclusion criteria of the diabetes PAD group: patients diagnosed as T2DM according to the above-mentioned diagnostic criteria for diabetes, and with (1) symptoms and signs of atherosclerotic occlusion (intermittent claudication, resting pain, reduced or absent pulsation of dorsal foot artery, etc.);(2) Ankle-brachial arterial pressure index (ABI) ≤0.9;Toe brachial artery pressure index (TBI) ≤0.70;There was no three-phase pulse pattern of foot artery.Transcutaneous partial oxygen pressure (TcPO2) <30mmHg;(3) Evidence of atherosclerosis, atherosclerotic plaques, arterial stenosis or obstruction in carotid and/or lower extremity major arteries found by vascular color Doppler ultrasound.
- Inclusion criteria for the diabetic foot group caused by PAD: the presence of infection, ulcer and/or deep tissue destruction of the foot was confirmed according to the above diagnostic criteria of diabetic PAD.
- Agree to participate in the study and data collection, and sign the informed consent.
Who cannot join
- -
- 1. Diabetic ketoacidosis or hyperosmolar state occurs within 30 days; Diabetic coma in 2 or 3 months, or severe hypoglycemia in nearly 1 month; 3. Diseases of tumor, immune system and hematopoietic system; 4. Other types of diabetes 5. Less than 40 years old
Trial locations and contacts
1 site in 1 country.
About this study
Diabetic foot disease with a global incidence of about 6% is one of the most serious complications of diabetes, which brings great pain and economic burden to patients.In China, the incidence rate is 8.1%, and the amputation rate is 7.3%. Every year, more than 1 million diabetic patients have amputations, ranking first among non-traumatic amputations.According to the American Diabetes Association (ADA), the incidence of Peripheral Arterial Disease (PAD) in diabetic patients is twice that of non-diabetic patients, and the resulting lower limb ischemia is the main cause of the high mortality and disability rate of diabetic foot.According to the International Working Group on Diabetic Foot (IWGDF), about 50% patients with diabetic foot disease are complicated with PAD, and the degree of vascular stenosis is closely related to the prognosis.Severe limb ischemia is a higher cause of diabetic foot ulcer in China than in western countries.Atherosclerosis is the main pathological change of diabetic peripheral artery disease, and endothelial injury is the initial link of atherosclerosis.Heat shock protein 90 (HSP90) is a kind of important heat stress protein, which accounts for about 2-3% of the total protein in cells.It is involved in the correct folding and activation of intracellular proteins.Although Hsp90 is primarily involved in intracellular protective mechanisms, they can also be exposed to the plasma membrane and released in the extracellular space, resulting in detectable levels of Hsp90 in the blood.Extracellular heat shock proteins are involved in cell-cell communication as well as immune and inflammatory processes.Hsp90 promotes cell survival, migration, inflammation and angiogenesis, and is therefore considered a promising target for cancer therapy.This led to the development of specific HSP90 inhibitors.More recently, these inhibitors have also been tested in diabetic animals.The use of the HSP90 inhibitor 17-DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype in a mouse model with hyperglycemia and hyperlipidemia.Hsp90 is upregulated in human carotid atherosclerotic plaques (especially in unstable areas of plaques) and in patients' serums, triggering autoimmune antibodies against Hsp90 in patients.Is HSP90 also present in serum of patients with diabetic peripheral arterial disease?Is there a relationship between secretory heat shock protein 90 and arterial disease?The study that HSP90 may be involved in the molecular mechanism of vascular endothelial barrier function impairment in diabetes will provide a new target for the early serological diagnosis and treatment of diabetic vascular disease.The aim of this study was to investigate the relationship between the degree of vascular disease and serum heat shock protein 90 in patients with type 2 diabetes.The study was divided into three groups: diabetic without PAD group, diabetic with PAD group and diabetic foot group.According to the degree of peripheral artery disease, the patients were divided into three groups, and the content of heat shock protein 90 in serum of the patients was detected.To analyze the correlation between the degree of peripheral arterial disease and the content of heat shock protein 90 in serum.
Read the detailed description
Diabetic foot disease with a global incidence of about 6% is one of the most serious complications of diabetes, which brings great pain and economic burden to patients.In China, the incidence rate is 8.1%, and the amputation rate is 7.3%. Every year, more than 1 million diabetic patients have amputations, ranking first among non-traumatic amputations.According to the American Diabetes Association (ADA), the incidence of Peripheral Arterial Disease (PAD) in diabetic patients is twice that of non-diabetic patients, and the resulting lower limb ischemia is the main cause of the high mortality and disability rate of diabetic foot.According to the International Working Group on Diabetic Foot (IWGDF), about 50% patients with diabetic foot disease are complicated with PAD, and the degree of vascular stenosis is closely related to the prognosis.Severe limb ischemia is a higher cause of diabetic foot ulcer in China than in western countries.Atherosclerosis is the main pathological change of diabetic peripheral artery disease, and endothelial injury is the initial link of atherosclerosis.Heat shock protein 90 (HSP90) is a kind of important heat stress protein, which accounts for about 2-3% of the total protein in cells.It is involved in the correct folding and activation of intracellular proteins.Although Hsp90 is primarily involved in intracellular protective mechanisms, they can also be exposed to the plasma membrane and released in the extracellular space, resulting in detectable levels of Hsp90 in the blood.Extracellular heat shock proteins are involved in cell-cell communication as well as immune and inflammatory processes.Hsp90 promotes cell survival, migration, inflammation and angiogenesis, and is therefore considered a promising target for cancer therapy.This led to the development of specific HSP90 inhibitors.More recently, these inhibitors have also been tested in diabetic animals.The use of the HSP90 inhibitor 17-DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype in a mouse model with hyperglycemia and hyperlipidemia.Hsp90 is upregulated in human carotid atherosclerotic plaques (especially in unstable areas of plaques) and in patients' serums, triggering autoimmune antibodies against Hsp90 in patients.Is HSP90 also present in serum of patients with diabetic peripheral arterial disease?Is there a relationship between secretory heat shock protein 90 and arterial disease?The study that HSP90 may be involved in the molecular mechanism of vascular endothelial barrier function impairment in diabetes will provide a new target for the early serological diagnosis and treatment of diabetic vascular disease.The aim of this study was to investigate the relationship between the degree of vascular disease and serum heat shock protein 90 in patients with type 2 diabetes.The study was divided into three groups: diabetic without PAD group, diabetic with PAD group and diabetic foot group.According to the degree of peripheral artery disease, the patients were divided into three groups, and the content of heat shock protein 90 in serum of the patients was detected.To analyze the correlation between the degree of peripheral arterial disease and the content of heat shock protein 90 in serum.
- Serum collection: the nurses collected the patients' fasting blood at 6:00 am in accordance with the routine blood collection procedures: 1 tube of procoagulant blood and 1 tube of anticoagulant blood were collected, each tube was no less than 3ml of blood;Store in a 4-degree refrigerator for disposal.
- Collection of serum and plasma: the blood samples collected by the nurse were placed in a centrifuge, centrifuged at 3000 RPM for 15 minutes, and then the supernatant was collected.
- Laboratory test: the collected serum or plasma were quantitatively tested by HSP90 ELISA, and the results were analyzed.The remaining serum or plasma was stored in a negative 80 refrigerator.
- Conditions
- Peripheral Arterial Disease
- Being tested
- non-intervention
- Keywords
- diabetic disease, peripheral arterial disease, Extracellular heat shock protein 90
- 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.
non-interventionOther
non-intervention
| Study group | Role | What they receive |
|---|---|---|
| diabetes without complications | diabetes without complications Receives: Other: non-intervention | |
| diabetes with Peripheral Arterial Disease | diabetes with Peripheral Arterial Disease Receives: Other: non-intervention | |
| diabetic foot group | diabetic foot group Receives: Other: non-intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heat shock protein 90
The serum heat shock protein 90 was detected
Measured: In December 2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start1 Sep 2020
- Primary completion10 Nov 2020
- Study completion10 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mengchen Zou, Principal investigator, labor relations
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04787770
- Sponsor's protocol ID
- NFEC-2020-268
- Acronym
- rhsppvlda
- Status last verified
- Jan 2021
- First submitted
- 4 Mar 2021
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ding X, Meng C, Dong H, Zhang S, Zhou H, Tan W, Huang L, He A, Li J, Huang J, Li W, Zou F, Zou M. Extracellular Hsp90alpha, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes. BMJ Open Diabetes Res Care. 2022 Jan;10(1):e002579. doi: 10.1136/bmjdrc-2021-002579.
PubMed 35091448
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of HSP90 in Peripheral Vascular Lesions of Diabetic Atherosclerosis
- ClinicalTrials.gov ID
- NCT04787770
- Acronym / sponsor ID
- rhsppvlda / NFEC-2020-268
- Conditions
- Peripheral Arterial Disease
- Keywords
- diabetic disease, peripheral arterial disease, Extracellular heat shock protein 90
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 10 Nov 2020 (actual)
- Study completion
- 10 Dec 2020 (actual)
- First posted
- 9 Mar 2021 (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.
Diabetic foot disease with a global incidence of about 6% is one of the most serious complications of diabetes, which brings great pain and economic burden to patients.In China, the incidence rate is 8.1%, and the amputation rate is 7.3%. Every year, more than 1 million diabetic patients have amputations, ranking first among non-traumatic amputations.According to the American Diabetes Association (ADA), the incidence of Peripheral Arterial Disease (PAD) in diabetic patients is twice that of non-diabetic patients, and the resulting lower limb ischemia is the main cause of the high mortality and disability rate of diabetic foot.According to the International Working Group on Diabetic Foot (IWGDF), about 50% patients with diabetic foot disease are complicated with PAD, and the degree of vascular stenosis is closely related to the prognosis.Severe limb ischemia is a higher cause of diabetic foot ulcer in China than in western countries.Atherosclerosis is the main pathological change of diabetic peripheral artery disease, and endothelial injury is the initial link of atherosclerosis.Heat shock protein 90 (HSP90) is a kind of important heat stress protein, which accounts for about 2-3% of the total protein in cells.It is involved in the correct folding and activation of intracellular proteins.Although Hsp90 is primarily involved in intracellular protective mechanisms, they can also be exposed to the plasma membrane and released in the extracellular space, resulting in detectable levels of Hsp90 in the blood.Extracellular heat shock proteins are involved in cell-cell communication as well as immune and inflammatory processes.Hsp90 promotes cell survival, migration, inflammation and angiogenesis, and is therefore considered a promising target for cancer therapy.This led to the development of specific HSP90 inhibitors.More recently, these inhibitors have also been tested in diabetic animals.The use of the HSP90 inhibitor 17-DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype in a mouse model with hyperglycemia and hyperlipidemia.Hsp90 is upregulated in human carotid atherosclerotic plaques (especially in unstable areas of plaques) and in patients' serums, triggering autoimmune antibodies against Hsp90 in patients.Is HSP90 also present in serum of patients with diabetic peripheral arterial disease?Is there a relationship between secretory heat shock protein 90 and arterial disease?The study that HSP90 may be involved in the molecular mechanism of vascular endothelial barrier function impairment in diabetes will provide a new target for the early serological diagnosis and treatment of diabetic vascular disease.The aim of this study was to investigate the relationship between the degree of vascular disease and serum heat shock protein 90 in patients with type 2 diabetes.The study was divided into three groups: diabetic without PAD group, diabetic with PAD group and diabetic foot group.According to the degree of peripheral artery disease, the patients were divided into three groups, and the content of heat shock protein 90 in serum of the patients was detected.To analyze the correlation between the degree of peripheral arterial disease and the content of heat shock protein 90 in serum.
Detailed description
Diabetic foot disease with a global incidence of about 6% is one of the most serious complications of diabetes, which brings great pain and economic burden to patients.In China, the incidence rate is 8.1%, and the amputation rate is 7.3%. Every year, more than 1 million diabetic patients have amputations, ranking first among non-traumatic amputations.According to the American Diabetes Association (ADA), the incidence of Peripheral Arterial Disease (PAD) in diabetic patients is twice that of non-diabetic patients, and the resulting lower limb ischemia is the main cause of the high mortality and disability rate of diabetic foot.According to the International Working Group on Diabetic Foot (IWGDF), about 50% patients with diabetic foot disease are complicated with PAD, and the degree of vascular stenosis is closely related to the prognosis.Severe limb ischemia is a higher cause of diabetic foot ulcer in China than in western countries.Atherosclerosis is the main pathological change of diabetic peripheral artery disease, and endothelial injury is the initial link of atherosclerosis.Heat shock protein 90 (HSP90) is a kind of important heat stress protein, which accounts for about 2-3% of the total protein in cells.It is involved in the correct folding and activation of intracellular proteins.Although Hsp90 is primarily involved in intracellular protective mechanisms, they can also be exposed to the plasma membrane and released in the extracellular space, resulting in detectable levels of Hsp90 in the blood.Extracellular heat shock proteins are involved in cell-cell communication as well as immune and inflammatory processes.Hsp90 promotes cell survival, migration, inflammation and angiogenesis, and is therefore considered a promising target for cancer therapy.This led to the development of specific HSP90 inhibitors.More recently, these inhibitors have also been tested in diabetic animals.The use of the HSP90 inhibitor 17-DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype in a mouse model with hyperglycemia and hyperlipidemia.Hsp90 is upregulated in human carotid atherosclerotic plaques (especially in unstable areas of plaques) and in patients' serums, triggering autoimmune antibodies against Hsp90 in patients.Is HSP90 also present in serum of patients with diabetic peripheral arterial disease?Is there a relationship between secretory heat shock protein 90 and arterial disease?The study that HSP90 may be involved in the molecular mechanism of vascular endothelial barrier function impairment in diabetes will provide a new target for the early serological diagnosis and treatment of diabetic vascular disease.The aim of this study was to investigate the relationship between the degree of vascular disease and serum heat shock protein 90 in patients with type 2 diabetes.The study was divided into three groups: diabetic without PAD group, diabetic with PAD group and diabetic foot group.According to the degree of peripheral artery disease, the patients were divided into three groups, and the content of heat shock protein 90 in serum of the patients was detected.To analyze the correlation between the degree of peripheral arterial disease and the content of heat shock protein 90 in serum.
- Serum collection: the nurses collected the patients' fasting blood at 6:00 am in accordance with the routine blood collection procedures: 1 tube of procoagulant blood and 1 tube of anticoagulant blood were collected, each tube was no less than 3ml of blood;Store in a 4-degree refrigerator for disposal.
- Collection of serum and plasma: the blood samples collected by the nurse were placed in a centrifuge, centrifuged at 3000 RPM for 15 minutes, and then the supernatant was collected.
- Laboratory test: the collected serum or plasma were quantitatively tested by HSP90 ELISA, and the results were analyzed.The remaining serum or plasma was stored in a negative 80 refrigerator.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| diabetes without complications | – | Other: non-interventiondiabetes without complications |
| diabetes with Peripheral Arterial Disease | – | Other: non-interventiondiabetes with Peripheral Arterial Disease |
| diabetic foot group | – | Other: non-interventiondiabetic foot group |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 150 cases, 50 cases in each group.
Key inclusion criteria (4 listed)
- Diagnostic criteria for diabetes: using WHO1999 diabetes diagnostic criteria, that is, (1) having diabetes symptoms (polyuria, polydipsia, and unexplained weight loss), and random (any time after meal) plasma glucose ≥11.1mmol/L(200mg/ dL);(2), or fasting (fasting for at least 8 hours) plasma glucose ≥7.0mmol/L(126mg/ dL);(3), or OGTT 2 hours plasma glucose ≥11.1mmol/L(200mg/ dL)
- Inclusion criteria of the diabetes PAD group: patients diagnosed as T2DM according to the above-mentioned diagnostic criteria for diabetes, and with (1) symptoms and signs of atherosclerotic occlusion (intermittent claudication, resting pain, reduced or absent pulsation of dorsal foot artery, etc.);(2) Ankle-brachial arterial pressure index (ABI) ≤0.9;Toe brachial artery pressure index (TBI) ≤0.70;There was no three-phase pulse pattern of foot artery.Transcutaneous partial oxygen pressure (TcPO2) <30mmHg;(3) Evidence of atherosclerosis, atherosclerotic plaques, arterial stenosis or obstruction in carotid and/or lower extremity major arteries found by vascular color Doppler ultrasound.
- Inclusion criteria for the diabetic foot group caused by PAD: the presence of infection, ulcer and/or deep tissue destruction of the foot was confirmed according to the above diagnostic criteria of diabetic PAD.
- Agree to participate in the study and data collection, and sign the informed consent.
Key exclusion criteria (2 listed)
- -
- 1. Diabetic ketoacidosis or hyperosmolar state occurs within 30 days; Diabetic coma in 2 or 3 months, or severe hypoglycemia in nearly 1 month; 3. Diseases of tumor, immune system and hematopoietic system; 4. Other types of diabetes 5. Less than 40 years old
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 |
|---|---|---|
| non-interventionnon-intervention | Other | diabetes with Peripheral Arterial Disease, diabetes without complications, diabetic foot group |
Primary outcome
Heat shock protein 90
Time frame: In December 2020
The serum heat shock protein 90 was detected
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 Mar 2021.
- Derived from this study: PubMed 35091448Ding X, Meng C, Dong H, Zhang S, Zhou H, Tan W, Huang L, He A, Li J, Huang J, Li W, Zou F, Zou M. Extracellular Hsp90alpha, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes. BMJ Open Diabetes Res Care. 2022 Jan;10(1):e002579. doi: 10.1136/bmjdrc-2021-002579.
- 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.
Mengchen Zou principal investigator
labor relations
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 Peripheral Arterial Disease, run by Nanfang Hospital, Southern Medical University 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 4 inclusion and 2 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 Mar 2021. 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?
Heat shock protein 90 (time frame: In December 2020). 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 NCT04787770, which also lists 1 linked publication.
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 Mar 2021.