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Trial registered on ANZCTR


Registration number
ACTRN12617000124336
Ethics application status
Approved
Date submitted
18/01/2017
Date registered
24/01/2017
Date last updated
2/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Insulin Pump therapy for Reducing Diabetic complications (InsPyReD) study
Scientific title
Efficacy of Insulin Pump Therapy for Reducing Diabetic complications in adults with type 1 diabetes (InsPyReD)
Secondary ID [1] 289014 0
nil
Universal Trial Number (UTN)
Trial acronym
InsPyReD Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 298425 0
Type 1 diabetes 298426 0
Diabetic Neuropathy 298427 0
Condition category
Condition code
Neurological 298520 298520 0 0
Neurodegenerative diseases
Metabolic and Endocrine 298521 298521 0 0
Diabetes
Eye 301402 301402 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible participants will be randomised to either control (standard multiple daily insulin injections) or the intervention group (insulin pump therapy) for a period of 2 years.

The intervention, insulin pump therapy (using model MMT-754 Medtronic MiniMed Paradigm Veo), will be administered at the Diabetes Centre at the Prince of Wales Hospital via standard clinical procedures; this typically involves intensive consultation with an Endocrinologist (Director of the Diabetes Centre and CIC, Dr Ann Poynten) and a nurse educator on pump use, in addition to multiple appointments to ensure pumps are calibrated appropriately to achieve glucose control whilst minimising risk of hypoglycaemic events. These appointments last about 1 hr and typically occur once a week for the first 2-3 weeks after pump initiation. Once pumps are calibrated appropriately, standard endocrinology follow-up appointments will occur for approximately 30 minutes at 6, 12, 18 and 24 months. At these time points, outcome measures for the trial will also be obtained and take approximately 1 hr.
Documentation provided: Participants will also be educated on the use of the pump in face to face appointments and provided with information and documentation specific to the model of the pump being implemented (provided as part of the standard commercial pump package). Participants will also be provided with contact details of the trial co-ordinator (Dr Natalie Kwai) and in the case of an emergency related to their diabetes, CIC Poynten's on-call contact details.
Intervention code [1] 294503 0
Prevention
Intervention code [2] 294504 0
Treatment: Devices
Comparator / control treatment
A control group (patients treated with a standard insulin injection regimen) will be monitored similarly to those in the intervention arm for comparison.
Control group
Active

Outcomes
Primary outcome [1] 298022 0
Corneal confocal microscopy will be used to determine the level of nerve damage in the eye. Nerve fiber density, length and tortuosity will be assessed.
Timepoint [1] 298022 0
6, 12, 18 AND 24 MONTHS ON INTERVENTION OR STANDARD CARE
Secondary outcome [1] 322910 0
Severity of Neuropathy will be assessed using the Total Neuropathy Score. The score consists of neurological clinical assessment of sensation, strength and nerve conduction studies.
Timepoint [1] 322910 0
6, 12, 18, 24 MONTHS ON INTERVENTION OR STANDARD CARE
Secondary outcome [2] 323019 0
Nerve Excitability Composite score.
Nerve excitability is a non invasive test which provides indication of intrinsic nerve function and involves using surface electrodes to stimulate a nerve in the wrist and record a response distally. A composite score of the Nerve Excitability parameters hyperpolarising threshold electrtonus (90-100ms), depolarising threshold electrotonus (10-20ms) and subexcitability will be used.
Timepoint [2] 323019 0
6, 12, 18, 24 MONTHS ON INTERVENTION OR STANDARD CARE
Secondary outcome [3] 330882 0
Neuropeptide Y concentration in patient tears.
Neuropeptide Y is released from corneal nerves in response to damage.
Timepoint [3] 330882 0
6, 12, 18, 24 MONTHS ON INTERVENTION OR STANDARD CARE
Secondary outcome [4] 330883 0
Neuropathy related quality of life.
Quality of life specific to neuropathy will be assessed using a validated tool termed the NeuroQoL Questionnaire (Vileikyte et al., 2003). NeuroQoL scores degree of symptom effect as a function of presence/frequency and level of bother.
Timepoint [4] 330883 0
6, 12, 18, 24 MONTHS ON INTERVENTION OR STANDARD CARE
Secondary outcome [5] 330884 0
Glucose Variability.
Glucose variability will be assessed in terms of Mean Amplitude of Glycaemic Excursions (Brownlee and Hirsch, 2006) using a continuous subcutaneous sensor. MAGE is calculated over a consecutive 48 hour period and participants will keep the sensor in situ for six days to ensure a consecutive 48 hours is captured in full.
Timepoint [5] 330884 0
At screening and trial closeout for enrolled participants.

Eligibility
Key inclusion criteria
History of type 1 diabetes, currently on multiple daily insulin injections but deemed suitable for continuous subcutaneous insulin infusions (CSII/Pump therapy) by treating endocrinologist. 18-45 years of age.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Previous insulin pump therapy
b. Severe neuropathy, leading to difficulty with performing neurophysiological assessments.
c. Administration of another investigational drug within 30 days prior to randomisation.
d. Significant neurological or psychiatric disorders.
e. History of other conditions aside from type 1 diabetes that cause neuropathy (e.g end stage kidney disease).
f. Known pregnancy.
g. Known medical history causing reduced corneal sensation and neurotrophic keratitis (e.g. viral infections, chemical burns, corneal surgery, excessive use of topical anaesthetic, history of fifth nerve palsy and multiple sclerosis).


Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The three excitability measures that comprise the primary endpoint (hyperpolarizing threshold electrotonus at 90-100 ms, depolarizing threshold electrotonus at 10-20 ms and subexcitability) can be combined into an excitability index using the linear coefficients (1,-1,-1 respectively). This results in index values ranging between 30 and 80 having an approximate normal distribution (standard deviation 11.6). Two groups of 30 patients randomly allocated to either CSII or MDII, would provide 80% power to detect a difference of up to 8.5 index points. The 3 measurements will be required on all patients. This study will enable evaluation of later neuropathy rates in these 2 groups. 95% confidence intervals for these groups will be no wider than (33%, 66%) if 15/30 patients go on to develop symptoms. Correlation with the index will be evaluated and inform its potential role as a surrogate marker for use in subsequent studies.
Methods of statistical analysis of finalised data will be adjusted for disease duration and HbA1c% between groups as these clinical parameters may differ between CSII and MDII-treated patients. Data will be described using standard statistical methods (mean and standard deviation, median and interquartile range or frequency and percentage, depending on the variable type) to characterise the patient population and their neurophysiological, clinical and patient-reported outcomes. Linear models, with adjustment for specified a priori factors including age, duration of diabetes, HbA1c% and pre-existing neuropathy will be used to examine associations between MAGE and both measures of axonal function and long-term development of clinical evident DPN.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5632 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 13085 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 293382 0
Commercial sector/Industry
Name [1] 293382 0
Medtronic Australasia
Address [1] 293382 0
5 Alma Road
Macquarie Park
NSW, 2113

N.B. This study is an investigator initiated project for which Medtronic is providing in-kind support
Country [1] 293382 0
Australia
Primary sponsor type
University
Name
University of New South Wales Australia
Address
UNSW Australia
Kensington
NSW 2052
Country
Australia
Secondary sponsor category [1] 292202 0
Hospital
Name [1] 292202 0
Prince of Wales Hospital
Address [1] 292202 0
Prince of Wales Hospital
Hight street
Randwick
NSW 2031
Country [1] 292202 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294840 0
Human Research Executive Committee South Eastern Sydney Local Health District
Ethics committee address [1] 294840 0
Research Support Office
G71, East Wing
Edmund Blacket Building
Prince of Wales Hospital
Avoca Street
Randwick NSW 2031
Ethics committee country [1] 294840 0
Australia
Date submitted for ethics approval [1] 294840 0
21/10/2015
Approval date [1] 294840 0
14/04/2016
Ethics approval number [1] 294840 0
15/058 (HREC/16/POWH/109)

Summary
Brief summary
This study aims to determine whether insulin pump therapy can prevent nerve injury in patients with type 1 diabetes

Who is it for?
You can join this study if you have type 1 diabetes, aged 18-45 years and have not received insulin pump therapy before

Trial details
In this study, participants are randomly (by chance) divided into two groups. One group will receive an insulin pump free of charge for a period of 2 years. The other group will receive standard insulin injection therapy. Participants will undergo non-invasive nerve and eye tests to determine their suitability for the trial and when enrolled, will undergo these follow-up assessments at 6, 12, 18 and 24 months, coinciding with their usual endocrinology appointments. Both groups will receive continuous glucose monitoring at the beginning and end of the trial to determine the effect of glucose variability on nerve function. Participants will also undergo assessments of their quality of life specific to any nerve damage they may have.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65206 0
Prof Arun Krishnan
Address 65206 0
Institute of Neurological Sciences
Level 2 High Street Building
High Street
Prince of Wales Hospital
Randwick NSW 2031
Country 65206 0
Australia
Phone 65206 0
+61 2 9382 2413
Fax 65206 0
Email 65206 0
arun.krishnan@unsw.edu.au
Contact person for public queries
Name 65207 0
Dr Natalie Kwai
Address 65207 0
Institute of Neurological Sciences
Level 2 High Street Building
High Street
Prince of Wales Hospital
Randwick NSW 2031
Country 65207 0
Australia
Phone 65207 0
+61 2 9382 2413
Fax 65207 0
Email 65207 0
natalie.kwai@unsw.edu.au
Contact person for scientific queries
Name 65208 0
Prof Arun Krishnan
Address 65208 0
Institute of Neurological Sciences
Level 2 High Street Building
High Street
Prince of Wales Hospital
Randwick NSW 2031
Country 65208 0
Australia
Phone 65208 0
+61 2 9382 2413
Fax 65208 0
Email 65208 0
arun.krishnan@unsw.edu.au

No information has been provided regarding IPD availability
Summary results
No Results