The Role of HSP90 in Peripheral Vascular Lesions of Diabetic Atherosclerosis
Conditions: Peripheral Arterial Disease
Sponsor: Nanfang Hospital, Southern Medical University

 
V1.0/2020-7-20 
  
Clinical study protocol 
 
 
Project title: Secreted heat shock protein 90 is involved in the 
pathogenesis of diabetic peripheral vascular disease 
Scheme version/date: v1.0/2020-7-20 
Research 
Department/Principal 
investigator: 
Department 
of 
Endocrinology and Metabolism/Mengchen Zou 
Sponsor/Address: Nanfang Hospital, Southern Medical University/No. 
1838, North Guangzhou Avenue, Baiyun District, Guangzhou 
 
 
 
 
 
 
 
 
 

 
V1.0/2020-7-20 
 
 
Confidentiality Statement: 
The information contained in this study protocol is provided for review only by 
the project investigator, the ethics committee, and relevant agencies. The copyright is 
owned by Nanfang Hospital of Southern Medical University. Without the approval of 
Nanfang Hospital of Southern Medical University, it is strictly prohibited to disclose 
any information to third parties unrelated to this study. 

 
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Summary of Research Scheme 
Package name 
The role of secretory heat shock protein 90 in the 
pathogenesis of diabetic peripheral vascular disease 
Bidding for 
the unit 
Nanfang Hospital, Southern Medical University 
Principal 
investigator 
Zou Mengchen 
Research 
center and 
responsible 
person 
Zou Mengchen, Nanfang Hospital, Southern Medical 
University 
The research 
object 
Ⅱ with type 1 diabetes 
Research 
purpose 
Main purpose: Ⅱ with type 1 diabetes, vascular lesion 
severity, and the relationship between heat shock protein 
90 in serum. 
Secondary purpose: serum heat shock protein 90 (HSP90) can predict 
the degree of vascular disease in diabetic patients. 
The research 
group 
The diabetic group had no PAD, had PAD, and had diabetic 
foot disease 
Study design 
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. 
The time limit The 2020-9-1-2020-9-1 
Sample size 
150 cases, 50 cases in each group. 
The inclusion 
criteria 
1. 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) 
2. 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 

 
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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. 
3. 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. 
4. Agree to participate in the study and data collection, 
and sign the informed consent. 
Exclusion 
criteria 
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 
Validity 
analysis 
The main observation indexes: Ⅱ with type 1 diabetes, 
serum content of heat shock protein 90. 
Statistical 
analysis 
Sample size determination:
 
 
Statistical analysis: SAS 9.2 statistical analysis 
software will be used for statistical analysis. 
follow-up 
No follow-up 
Statistical 
method 
Analysis of variance 
schedule 
2020-9-1 -- 2020-10-10 Collect all samples 
2020-10-10 -- 2020-10-15 Complete all sample tests 
2020-10-15 -- 2020-10-20 Statistical analysis was 
completed 

 
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List of abbreviations and definitions of terms 
Arterial lesions around PAD 
OGTT oral glucose tolerance test 

 
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1. Research background 
Diabetic foot disease is one of the most serious complications of 
diabetes, which brings great pain and economic burden to patients, with 
a global incidence of about 6%.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. The main 
pathological change of diabetic PAD is atherosclerosis, and endothelial 
injury is the initial link of atherosclerosis.Oxidative stress is the 
central link in the mechanism of endothelial injury in diabetic 
vascular disease, and it is also the basis for us to model endothelial 
cells with high glucose and hydrogen peroxide. 
Heat Shock Protein 90 (Hsp90) is an important type of Heat stress 
Protein. The molecular size of Hsp90 is 90-kDa. In eukaryotic cells, 
there are mainly two subtypes, α and β, and the content of Hsp90 
accounts for 2-3% of the total Protein in cells.Involves 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 

 
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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. 
2. Research Objectives 
Main purpose: 2.1 Ⅱ with type 1 diabetes, vascular lesion severity, and the 
relationship between heat shock protein 90 in serum.  
2.2 Secondary purpose: serum heat shock protein 90 was used to predict the 
degree of vascular disease in diabetic patients.  
3. Study endpoint 
3.1 Primary end point: Patients were screened for diabetic angiopathy during 
hospitalization. 
4. Study design 
This study is a prospective study. It is planned to enroll 150 subjects, with 50 
subjects in each group. 
Subjects will not be given or offered any randomization or any study regimen-
driven treatment during the study.If it is clinically applicable, treatment decisions and 
treatment options are made at the discretion of the treating physician. 
5. Subjects 
The subjects of this study is Ⅱ crowd with type 1 diabetes. 
Diagnostic criteria: 5.1 reference WHO1999 years diabetes diagnosis standard, 
specification and so on carries on the diagnosis of Ⅱ with type 1 diabetes.  
5.2 Inclusion criteria:  

 
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Voluntarily signed informed consent; 
Over 40 years of age, regardless of gender 
WHO1999 year after the diagnosis of diabetes guidelines, specifications Ⅱ 
diagnosed with type 1 diabetes 
5.3 Exclusion criteria:  
 Diabetic ketoacidosis or hyperosmolar state occurs within 30 days; 
 Diabetic coma in 3 months, or severe hypoglycemia in nearly 1 month; 
 Diseases of tumor, immune system and hematopoietic system; 
 Other types of diabetes 
 The researcher judged that it was not suitable to participate in this study. 
5.4 Case withdrawal and abscission 
All enrolled subjects have the right to withdraw from the study at any time.Case 
withdrawal reasons: 
−The subject requested to withdraw and did not want to continue in this study; 
−For other reasons, the investigator determined that subjects were not 
appropriate to continue in the study; 
Subjects who dropped out of the study were considered to have fallen out.When 
the patient falls off, try to contact the patient, complete the evaluation project, and fill 
in the study summary page. 
6. Research methods and procedures  
Because this is an observational study, no additional visits or laboratory analysis 
or evaluation beyond what is required by routine clinical practice are required. The 
doctor will decide the treatment plan according to the instructions and local 
regulations.   The investigator will review the patient's medical history and 
laboratory reports to determine eligibility based on inclusion and exclusion criteria. 
Patients must sign the latest IRB/ IEC-approved informed consent form (ICF) prior to 
performing data collection.The number and duration of visits are at the discretion of 
the physician in accordance with local practice. 
6.1 Informed consent and inclusion  
Subjects who provide informed consent and meet all other inclusion/exclusion 

 
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criteria are considered to be enrolled in the study. 
6.2 Subject identification number  
Each subject was given a unique identification number, namely the initials of 
the patient and the serial number. The identification numbers of the diabetic group 
without PAD were: DM001, DM002......And so on;The identification numbers 
of PAD groups are DMP001 and DMP002......And so on;The identification 
numbers of diabetic foot disease group were: DF001, DF002.......       
All study documents (such as case report forms, clinical records, etc.) will use this 
identification number.In addition, under data privacy regulations, a unique 
identification number is allowed, as long as it does not contain combined 
information that identifies the subject. 
6.3 Data source/data collection process 
Data from this study were obtained by extracting routine clinical records of 
enrolled subjects. The investigator was required to complete the study's electronic 
case report form (eCRF) and/or record form based on the information entered in the 
patient's medical record throughout the monitoring period. 
6.4 Data collection steps: 
6.4.1 screening period 
（1） Signed Informed Consent 
（2） Complete inclusion and exclusion criteria verification 
（3） Medical history and demographic data were obtained 
（4） Laboratory tests: screening for 
diabetes-related 
complications, blood routine, CRP, coagulation function, 
renal function, etc 
6.4.2 trial 
(1) 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 

 
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r e f r i g e r a t o r  f o r  d i s p o s a l .  
( 2 )  C o l l e c t i o n  o f  s e r u m  a n d  p l a s m a :  t h e  b l o o d  s a m p l e s  c o l l e c t e d  b y  
t h e  n u r s e  w e r e  p l a c e d  i n  a  c e n t r i f u g e ,  c e n t r i f u g e d  a t  3 0 0 0  R P M  f o r  
1 5  m i n u t e s ,  a n d  t h e n  t h e  s u p e r n a t a n t  w a s  c o l l e c t e d .  
( 3 )  L a b o r a t o r y  t e s t :  t h e  c o l l e c t e d  s e r u m  o r  p l a s m a  w e r e  q u a n t i t a t i v e l y  
t e s t e d  b y  H S P 9 0  E L I S A ,  a n d  t h e  r e s u l t s  w e r e  a n a l y z e d . T h e  r e m a i n i n g  
s e r u m  o r  p l a s m a  w a s  s t o r e d  i n  a  n e g a t i v e  8 0  r e f r i g e r a t o r .  
6 . 4 . 3  f o l l o w
6 . 4 . 3  f o l l o w - u p
u p  
A t el e p h o n e i nt er vi e w will b e c o n d uct e d ev er y 3 m o nt hs t o ass ess t h e p ati e nt's 
pr o g n osis ( bl o o d gl uc os e a n d m e dic ati o n st at us, c o m plic ati o n pr o gr essi o n, P A D or 
di a b etic f o ot dis e as e).  
7. S af et y m o nit ori n g, r e p orti n g a n d m e dic al tr e at m e nt  
7. 1 D efi niti o n of a d v ers e e v e nt ( A E)  
A n a d v ers e ev e nt is a ny a d v ers e m e dic al ev e nt t h at occ urs aft er a p ati e nt or 
s u bj ect r ec ei v es a dr u g a n d is n ot n ec ess arily c a us e- a n d-eff ect r el at e d t o t h e 
tr e at m ent. T h us, a n a d v ers e ev e nt c a n b e a ny a d v ers e p hysic al si g n (i ncl u di n g 
a b n or m al l a b or at or y r es ults), sy m pt o m, or dis e as e t h at is ti m e r el at e d t o t h e us e of 
t h e st u d y dr u g, r e g ar dl ess of w h et h er a c a us al r el ati o ns hi p wit h t h e st u d y dr u g is 
c o nsi d er e d. A d v ers e ev e nts i ncl u d e S eri o us A d v ers e ev e nts ( S A E) a n d n o n-s eri o us 
A d v ers e ev e nts.  
7. 2 t h e S A E d efi niti o n  
A S A E is a m e dic al ev e nt t h at occ urs d uri n g a cli nic al st u d y t h at r e q uir es or 
pr ol o n gs h os pit aliz ati o n, is dis a bl e d, aff ects w or k a bilit y, e n d a n g ers lif e or d e at h, or 
r es ults i n birt h d ef ects.I ncl u d es t h e f oll o wi n g m e dic al ev e nts: 
 1) d e at h ev e nts;  
 2) lif e -t hr e at e ni n g ev e nts ( d efi n e d as t h e s u bj ects of t h e att ac k, t h er e is i m m e di at e 
d a n g er of d e at h);  
 3) r e q uiri n g h os pit aliz ati o n or ext e n d t h e l e n gt h of  ti m e of ev e nts; 

 
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 4) c a n l e a d t o p er m a n e nt or s ev er e dis a bilit y/f u ncti o n/ ev e nt aff ects t h e a bilit y t o 
w or k;  
 5) a n o m al y or birt h d ef ects;  
 ot h er i m p ort a nt m e dic al ev e nt ( d efi n e d as ev e nts h ar m t o s u bj ects, or a ny n e e d t o 
i nt er v e n e t o pr ev e nt t h e a b ov e sit u ati o n).   
7. 3. R ec or di n g, c oll ecti n g, r e p orti n g a n d h a n dli n g of a d v ers e e v e nts  
7. 3. 1 C oll ecti o n, r e p orti n g a n d pr oc essi n g of A E  
Aft er si g ni n g t h e I nf or m e d C o ns e nt, all A Es t h at occ ur i n r el ati o n t o t h e 
pr escri b e d o p er ati n g pr oc e d ur es of t h e st u d y pr ot oc ol will b e r ec or d e d i n t h e e C R F.  
A r ec or d of A E s h o ul d i ncl u d e a d escri pti o n of A E a n d all r el at e d sy m pt o ms, ti m e 
of occ urr e nc e, s ev erit y, d ur ati o n, acti o n t a k e n, a n d fi n al o utc o m e a n d o utc o m e. T h e 
A E s h o ul d b e r ec or d e d i n m e dic al t er ms, a n d if t h e sy m pt o ms a n d si g ns of a s u bj ect 
c a n b e s u m m ariz e d by a c o m m o n c a us e, t h e di a g n osis s h o ul d b e r ec or d e d w h e n ev er 
p ossi bl e. Wit h t h e exc e pti o n of pr o gr essi o n -r el at e d i n dic at ors, all cli nic al ev e nts a n d 
cli nic ally si g nific a nt l a b or at or y a d v ers e ev e nts w er e tr e at e d ac c or di n g t o t h e 
C o m m o n Ev e nt Ev al u ati o n Crit eri a ( C T C A E) v ersi o n 5. 0.  
7. 3. 2 S A E c oll ecti o n a n d r e p orti n g  
All S A E i nci d e nts, r e g ar dl ess of c a us e, fr o m t h e d at e t h e s u bj ect si g n e d t h e 
i nf or m e d c o ns e nt will b e r e p ort e d usi n g t h e S A E R e p ort F or m.I n t h e ev e nt of S A E, 
t h e i nv esti g at or s h o ul d i m m e di at el y t a k e a p pr o pri at e tr e at m e nt m e as ur es t o e ns ur e 
t h e s af et y of t h e s u bj ects. 
7. 3. 4 D et er mi ni n g crit eri a f or s ev erit y of A E  
S ev erity will b e ass ess e d a g ai nst t h e fi v e -l ev el crit eri a d ev el o p e d by t h e N CI 
C T C A E 5. 0:  
■ Gr a d e 1, mil d; N o sy m pt o ms or mil d si g ns; F or cli nic al or di a g n ostic 
o bs er v ati o n o nl y, n o m e dic al i nt er v e nti o n is r e q uir e d;  
■ L ev el 2, m e di u m; A g e-a p pr o pri at e li mit ati o ns i n d ail y li vi n g f u ncti o ns (s uc h as 
c o o ki n g, s h o p pi n g, m a ki n g p h o n e c alls, etc.); 
■ L ev el 3, s eri o us or m e dic all y i m p ort a nt b ut n ot i m m e di at el y lif e -
t hr e at e ni n g; R es ulti n g i n or pr ol o n gi n g h os pit aliz ati o n; Dis a bl e d; R estrict e d d ail y s elf-

 
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care activities (daily self-care activities refer to bathing, dressing, undressing, eating, 
going to the toilet, taking medicine, etc., but not being bedridden); 
■ Level 4, life-threatening and requiring emergency treatment;  
■ Level 5, AE-related deaths  
7.3.5 Other responsibilities of the investigator during follow-up of serious adverse 
events  
Serious adverse events should be examined and treated according to clinical 
judgment, including necessary clinical laboratory tests, physical examinations, etc. 
The results of any examination or other updated SAE information must be followed 
up for the same time frame and procedure as the initial report. 
8. Study termination/suspension criteria 
8.1 Sponsor reserves the right to terminate/suspend the study.Before 
terminating/suspending a clinical study, the sponsor must notify the investigator, the 
ethics committee and the relevant regulatory authorities and state the reasons.After 
early termination/suspension of the study, study resumption must be reviewed and 
approved by the ERB. 
8.2 Termination/Suspension as required by the IRB. 
9. Provision for the termination of clinical studies 
The study ended when all subjects met the following criteria: 
1）All subjects completed at least a routine diabetes test 
2）2) or death, loss of follow-up or withdrawal of informed consent of all subjects. 
Data management 
10.1 Data management 
1) The researcher must ensure the authenticity, integrity and accuracy of the data;  
2) When making any corrections to the research records, only the underlined and 
the modified data should be annotated with reasons, signed and dated by the 
researcher, and the original records should not be erased or overwritten;  
3) Complete laboratory inspection items.  
10.2. Data recording and file preservation  
Subject data on the Case Report Form shall be recorded as Subject Numbers and 

 
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Subject can only be identified by Subject Numbers or their initials. 
OC-RDC was used for data management.   From the data entry to the 
verification requirements of the source data to the query and answer of the quality 
control data, finally to the operation of the data locking and export, 
After confirming that the data is in doubt, the parties sign the database lock 
application form and the database is locked by the data administrator. After the 
database is locked, the analysis database is exported by the data administrator and 
sent to the statisticians for statistical analysis. The locked data cannot be edited again, 
and problems found after database locking can be corrected in the statistical analysis 
program after confirmation. 
11. Statistical analysis 
11.1 Sample size determination 
This study was a non-interventional prospective study, and the scientific formula 
of sample size was estimated around the content of serum heat shock protein 90 in 
patients with diabetes.According to the statistical principle, the number of cases 
needed to achieve the desired purpose of the study was calculated as 50 cases in each 
group. 
11.2 Statistical methods 
The analysis included baseline analysis and analysis of the relationship between 
the degree of vascular disease and serum HSP90. 
11.3 Statistical Software and General Requirements: 
All statistical analyses were performed using SAS9.2 (or higher). 
The measurement data were described as mean, standard deviation and 
group number. 
12. Research management 
12.1 Comply with the requirements of relevant laws and regulations 
1) Investigators shall implement quality control and quality assurance systems for 
clinical studies using standard operating procedures; 
2) The original data must comply with the requirements of relevant laws and 
regulations;  

 
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3) Laboratory test results must be accurate and reliable;  
4) The observations and findings used should be verified to ensure the reliability 
of the data;  
5) Establish a complete research organization and clarify the responsibilities of 
personnel at all levels;  
6) The main researcher shall be responsible for overall quality control and carry 
out the responsibilities of personnel at all levels;  
7) The principal investigator shall be responsible for designing the study plan and 
informed consent, and the principal investigator shall write the study summary report 
after the study is over;  
8) The designated researcher shall be responsible for formulating the research 
implementation rules and SOP for use in the research;  
9) Before the study, the research team shall organize the study program for all 
participants, and all participants shall receive GCP training;  
10) Doctors and nurses participating in the study should strictly abide by the 
program provisions and follow the procedures without any arbitrary changes;  
11) The designated statistician shall be responsible for overall statistical 
processing of data.  
12.2 Subject's privacy shall be protected 
Subjects during the study period of completely confidential data entry computer 
storage and analysis, the necessary customs agency may to audit records, in order to 
verify that the true, accurate and integrity of the data, the research data may also be 
published in the academic journal, but participants name will not be published, the 
privacy of the subjects to be confidential. 
12.3 Problems occurred in the study and their treatment measures 
1) Revision of the scheme: After the scheme has been approved by the ethics 
committee, if the plan is to be revised, the "Revision Description of the Scheme" shall 
be formulated and signed by the principal investigator. Only after the researcher and 
the drug registration applicant have negotiated and agreed to revise the scheme; 
2) The revised scheme shall be submitted to the Ethics Committee for review and 

 
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approval before it can be implemented;  
3) No participant in the study shall violate the protocol.  
12.4 Quality control and quality assurance 
12.4.1 Quality assurance: 
The sponsor, entrusted by the sponsor is responsible for all or part of this study 
related responsibilities and tasks of the cooperation unit (including CRO, SMO, 
statistics institutions and clinical center, etc.) shall establish its own quality assurance 
system, to perform their respective duties, and strictly follow the clinical study scheme, 
adopt the corresponding standard operating procedures, to ensure the clinical 
research on the implementation of the quality control and quality assurance system. 
12.4.2 Quality assurance of clinical study process 
Before the start of clinical study, researchers should receive training on the study 
protocol, so that researchers can fully understand and recognize the specific 
connotations of the clinical study protocol and its indicators.The quality control 
personnel shall check the basic conditions of the clinical study to ensure that the 
clinical study conditions can meet the requirements of the protocol.During the study, 
researchers should conscientiously carry out clinical operations according to the 
requirements of the institution's SOP and the study protocol, and make true, timely, 
complete and standardized records.The quality control personnel will check the quality 
of the research process and the corresponding original records.After the end of the 
study, the research unit will sort out the corresponding project documents, which will 
be archived and stored after being checked by the quality control personnel.The 
quality assurance department of the clinical research unit checks the feasibility of the 
research carried out.When the non-conformance is found, the researcher and the 
person in charge of the unit shall be informed to make corrections in time, and the 
correction shall be tracked. 
12.4 Anticipated progress and completion date of the clinical study 
2020-9-1 -- 2020-10-10 Collect all samples 
2020-10-10 -- 2020-10-15 Complete all sample tests 
2020-10-15 -- 2020-10-20 Statistical analysis was completed 

 
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12.5 Responsibilities and other relevant work undertaken by the Parties 
1) Sponsor Responsibilities 
The sponsor is responsible for initiating, applying for, organizing, and funding 
the clinical study. 
2) Investigator responsibilities 
The investigator will conduct the clinical study in accordance with the ethical, 
ethical and scientific principles as well as protocol design and regulations laid down 
in the Declaration of Helsinki and relevant regulations. The investigator should be 
aware of the procedures and requirements for reporting SAE and should document 
and report these events as required.The investigator shall accurately, completely, 
timely and legally record the data into the eCRF and accept the inspection or 
inspection by the inspector or inspector dispatched by the sponsor or CRO company 
and the inspection and inspection by the pharmaceutical regulatory department to 
ensure the quality of the clinical study. 
3) Sponsor research methods for data publication 
Sponsor has exclusive rights to the research data. The final report should not be 
published on an individual's behalf until it is completed, unless it has been agreed in 
writing by the Sponsor or is reflected in the Co-operation Agreement.The sponsor has 
the final say regarding the manuscript and publication. 
12.6 The collection, sale, export and exit of human genetic resources shall comply 
with the Interim Measures for the Management of Human Genetic Resources (Guo 
Ban Fa [1998] No. 36). 
13. Research the relevant ethics 
13.1 Ethics Committee 
Prior to the commencement of the study, the investigator will submit the 
investigator's manual, study protocol, informed consent, CRF (based on actual 
submission), and any other information given to the subject to the IRB for 
approval.Any amendments to the study protocol must be approved by the IRB. 
13.2 Informed Consent 
The qualified investigator must explain in detail to each subject in informed 

 
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consent the nature, purpose, procedures, expected time, potential risks and benefits, 
and any discomforts that may arise of the study.Each subject must be aware that 
participation in the study is voluntary and that he/she may withdraw from the study 
and withdraw informed consent at any time without affecting his/her subsequent 
treatment or relationship with the treating physician. 
Informed consents should be given in standard written form and in non-
professional language as far as possible. Each informed consent must include all of the 
above and include a voluntary statement. The informed consent must be submitted to 
the ethics committee for approval. 
After the basic content of the study has been explained and the Investigator has 
satisfied that each prospective subject understands the purpose of the study, each 
prospective subject shall be required to sign and date the informed consent form.The 
subject should read and consider the statement before signing and dating it, and 
should obtain an informed consent to keep after signing. Without Informed Consent 
Subjects will not be admitted to the study without signing informed consent. 
13.3 other 
When a subject is unable to participate in informed consent independently, a 
reliable fair witness/legal representative must be present throughout the informed 
consent process.The selection of fair witness/legal representative shall not violate the 
subject's right to confidentiality.Upon the subject's oral consent, the fairness 
witness/legal representative should sign and date the informed consent to prove that 
the information is accurate. 
14. References 
 
 

 
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Clinical study protocol confirmation signature page 
 
 
 
The role of secretory heat shock protein 90 in the pathogenesis of 
diabetic peripheral vascular disease 
 
 
 
Principal Investigator's Consent on the Scheme: 
I have read this plan carefully, and I agree that it contains all the information 
necessary to carry out the research, and I agree to carry out the plan as described. I 
understand that the research shall not be initiated without the approval of the ethics 
committee, and shall fully comply with the relevant regulations of the unit. 
Informed consent forms and corresponding documentation of all participants 
should be obtained. Following the signing of the Informed Consent, clinical studies 
will be conducted in accordance with the requirements of the Declaration of Helsinki 
and the laws and regulations governing the clinical application of the research 
techniques. 
 
 
 
 
Signature of Principal Investigator: Date: