Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617000240347p
Ethics application status
Submitted, not yet approved
Date submitted
28/11/2016
Date registered
16/02/2017
Date last updated
16/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Novel markers of diabetes related kidney complications.
Scientific title
Isolation and characterisation of endothelial and urinary extracellular vesicles to identify potential biomarkers for diabetes and diabetic nephropathy.
Secondary ID [1] 290634 0
BIDI-2016-09-688
Universal Trial Number (UTN)
Trial acronym
not applicable
Linked study record
not applicable

Health condition
Health condition(s) or problem(s) studied:
diabetes related kidney disease 301152 0
Condition category
Condition code
Metabolic and Endocrine 300920 300920 0 0
Diabetes
Renal and Urogenital 301720 301720 0 0
Kidney disease

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study involves a screening visit to establish eligibility to the study based on presence or absence of diabetes status, renal impairment and macroalbuminia; and then a follow-up visit for blood and urine collection for isolation and characterisation of endothelial and urinary extracellular vesicles.


Comparisons will be made between three groups:
group 1 - type 2 diabetes, renal impairment [eGRF <60 ml/min] and no macroalbuminuria; group 2 - type 2 diabetes, renal impairment [eGFR <60 ml/min[ and macroalbuminuria
group 3 - no type 2 diabetes, no renal impairment [eGFR = to or > 60 ml/min] and no macroalbuminuria
Intervention code [1] 296515 0
Not applicable
Comparator / control treatment
control group is "health controls without diabetes" defined as no type 2 diabetes, no renal impairment [eGFR = to or > 60 ml/min], and no macroalbuminuria
Control group
Active

Outcomes
Primary outcome [1] 300332 0
To determine the viability of identifying extracellular vesicles
i) from urine (exosomes)
ii) from plasma (microvesicles)
as biomarkers for diabetic nephropathy.
Timepoint [1] 300332 0
cross-sectional study with testing undertaken at the time of blood and urine sample collection
Secondary outcome [1] 331683 0
To determine if there are differences in extracellular vesicles from
i) urine
ii) plasma
between patients with diabetic nephropathy and healthy controls.
Timepoint [1] 331683 0
cross-sectional study with testing undertaken at the time of blood and urine sample collection

Eligibility
Key inclusion criteria
(i) type 2 diabetes cohort
1. age 18-75 years
2. type 2 diabetes mellitus
with macroalbuminuria (urinary albumin:creatine = to or > 30mg/mmol and renal impairment (eGFR < 60 ml/min)
without albuminuria (urinary albumin:creatine < 3mg/mmol) but with renal impairment (eGFR < 60 ml/min)

(ii) healthy cohort
1. age 18-75 years
2. no type 2 diabetes
without albuminuria (urinary albumin:creatine < 3mg/mmol) but without renal impairment (eGFR = to or > 60 ml/min)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
(i) type 2 diabetes cohort
1. pregnant females
2. known renal/renal tract disease other than diabetic nephropathy

(ii) healthy cohort
1. presence of any diabetes including history of gestational diabetes mellitus
2. presence renal impairment (eGFR < 60 ml/min)
3. known renal/renal tract disease other than diabetic nephropathy
4. pregnant females

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Differences between the three categories of participants (no type 2 diabetes/normal renal function/no albuminuria versus type 2 diabetes/renal impairment/no albuminuria versus type 2 diabetes/renal impairment/albuminuria) on baseline participant characteristics, and exosome and microvesicle amount and composition, will be by:
(i) ANOVA for continuous variables
(ii) chi2 test/Fisher exact for categorical variables.

The impact of clinical and biochemical factors on exosome and microvesicle amount and composition will be by:
(i) Pearson r correlation for normally distributed variables
(ii) Spearman rank correlation for non-normally distributed variables.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2017
Actual
Date of last participant enrolment
Anticipated
31/10/2017
Actual
Date of last data collection
Anticipated
31/10/2017
Actual
Sample size
Target
55
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 295068 0
Commercial sector/Industry
Name [1] 295068 0
CSL Limited
Country [1] 295068 0
Australia
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
75 Commercial Road, Melbourne, Victoria 3004, Australia
Country
Australia
Secondary sponsor category [1] 293878 0
None
Name [1] 293878 0
Address [1] 293878 0
Country [1] 293878 0
Other collaborator category [1] 279325 0
Individual
Name [1] 279325 0
Dr David Greening
Address [1] 279325 0
La Trobe University, Kingsbury Drive, Bundoora, Victoria 3086, Australia
Country [1] 279325 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 296410 0
Bellberry
Ethics committee address [1] 296410 0
129 Glen Osmond Road, Eastwood South Australia 5063, Australia
Ethics committee country [1] 296410 0
Australia
Date submitted for ethics approval [1] 296410 0
28/11/2016
Approval date [1] 296410 0
Ethics approval number [1] 296410 0

Summary
Brief summary
Cells release diverse types of small membrane vesicles called exosomes and microvesicles and collectively are known as extracellular vesicles. Exosomes have an endocytic origin and are released upon multivesicular body fusion with the plasma membrane. Microvesicles are released from the cell surface, and are a rich source of non-conventionally secreted proteins lacking a conventional signal peptide, and thus not secreted by the classical secretory pathways. Both types of extracellular vesicles play major roles in intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids and RNA.

These extracellular vesicles are fragments of virtually all cell types (mainly endothelium, platelets, leukocytes) released into all types of body fluids during cell apoptosis or cell activation. They are characterised by an integral plasma membrane containing a subset of proteins, lipids and nucleic acids that are derived from the cell from which they originated. Extracellular vesicles may have important roles in intercellular communication, both locally and systemically, by transferring their contents between cells. Endothelial microvesicles play key roles in coagulation, inflammation and angiogenesis and can be quantified by flow cytometry using specific endothelial markers.

Diabetic nephropathy is a prevalent major microvascular complication defined by functional, structural and clinical abnormalities of the kidney that is caused by diabetes. This complication has become the most frequent cause of end-stage renal disease. Additionally, it is strongly associated with cardiovascular morbidity and mortality. Diagnosis is usually based on the measurement of high levels of albumin in the urine and evidence of reduced kidney function.
Trial website
not applicable
Trial related presentations / publications
none to date
Public notes
nil

Contacts
Principal investigator
Name 70798 0
A/Prof Esther Briganti
Address 70798 0
Baker Heart and Diabetes Institute
Level 4, 99 Commercial Road, Melbourne Victoria 3004, Australia
Country 70798 0
Australia
Phone 70798 0
+61 3 8532 1838
Fax 70798 0
+61 3 8532 1899
Email 70798 0
[email protected]
Contact person for public queries
Name 70799 0
A/Prof Esther Briganti
Address 70799 0
Baker Heart and Diabetes Institute
Level 4, 99 Commercial Road, Melbourne Victoria 3004, Australia
Country 70799 0
Australia
Phone 70799 0
+61 3 8532 1838
Fax 70799 0
+61 3 8532 1899
Email 70799 0
[email protected]
Contact person for scientific queries
Name 70800 0
A/Prof Esther Briganti
Address 70800 0
Baker Heart and Diabetes Institute
Level 4, 99 Commercial Road, Melbourne Victoria 3004, Australia
Country 70800 0
Australia
Phone 70800 0
+61 3 8532 1838
Fax 70800 0
+61 3 8532 1899
Email 70800 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.