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Trial registered on ANZCTR


Registration number
ACTRN12617000780358
Ethics application status
Approved
Date submitted
4/05/2017
Date registered
29/05/2017
Date last updated
29/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Preventing the neurotoxic effects of hypoglycaemia in adolescents with Type 1 diabetes- a randomised placebo-controlled trial
Scientific title
Efficacy of medium chain triglycerides (MCT) for preventing the neurotoxic effects of hypoglycaemia in adolescents with Type 1 diabetes- a randomised placebo-controlled trial
Secondary ID [1] 291854 0
Nil
Universal Trial Number (UTN)
U1111-1196-2906
Trial acronym
MCT Diabetes Trial
Linked study record


Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 303110 0
Hypoglycaemia 303140 0
Condition category
Condition code
Metabolic and Endocrine 302568 302568 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a non-drug intervention crossover trial, which instead uses a dietary supplement MCT. All participants will be assessed using the combination of a hyperinsulinaemic clamp, functional MRI and cognitive testing on 2 occasions: I) with ingestion of MCT and ii) with ingestion of placebo.
The MCT mixture that will be used will be Liquigen (Nutricia), 50% MCT emulsion (compromising 55% octanoate, 36% decanoate and 9% other fatty acids). A single 40g dose (83ml) will be ingested over 10 min.
An experienced dietician will be in charge of distributing the MCT/Placebo into opaque drinking cups with a lid and hard plastic straws to ensure blinding occurs.

The two arms will be separated by at least 1 week but no longer than 6 weeks.


The participants will be block allocated. The MRI scans & cognitive testing will be done prior to either the MCT or placebo, and post the participant drinking the placebo/MCT. The participant will then be required to attend another day, within 6 weeks of the first session, and the same process will happen again. Thus one day will be a placebo drink the other day will be the MCT drink.
Intervention code [1] 297963 0
Prevention
Comparator / control treatment
Randomised placebo controlled trial. The placebo will be made up of water and thickener
Control group
Placebo

Outcomes
Primary outcome [1] 301986 0
The primary outcome is arterial spin labelling (ASL), a non invasive measure of cerebral blood flow, during experimentally induced hypoglycaemia following I) MCT and ii) placebo
Timepoint [1] 301986 0
60- 15 minutes prior to administration of MCT/placebo a MRI scan of the brain will be used as baseline, 60- 105 minutes post administration of MCT/Placebo a MRI scan will assess the brain,
Secondary outcome [1] 334445 0
Blood oxygen level dependent (BOLD) signal will be used to assess both metabolic activity and functional connectivity of the brain
Timepoint [1] 334445 0
60- 15 minutes prior to administration of MCT/placebo a MRI scan of the brain will be used as baseline, 60- 105 minutes post administration of MCT/Placebo a MRI scan will assess the brain,
Secondary outcome [2] 334503 0
Cogstate aggregate scores to assess neurocognitive function
Timepoint [2] 334503 0
.15 minutes prior to administration of MCT up to 0 minutes cognitive testing using Cogstate will be done as a baseline on computer in adjacent room

At 105-115 minute post administration cognitive testing using Cogstate will happen off a portable computer in the room adjacent to the MRI.

180-190 minutes post administration of MCT/placebo cognitive testing using Cogstate will occur
Secondary outcome [3] 335271 0
Magnetic resonance spectroscopy will assess aspects of higher neurocognitive function
Timepoint [3] 335271 0
60- 15 minutes prior to administration of MCT/placebo a MRI scan of the brain will be used as baseline, 60- 105 minutes post administration of MCT/Placebo a MRI scan will assess the brain,
Secondary outcome [4] 335272 0
Serum ketone levels will assess the degree of ketonemia generated
Timepoint [4] 335272 0
This will be done at 15 minute intervals for 3 hours post administration of MCT/placebo using keytone strips
Secondary outcome [5] 335273 0
Self reported symptoms of hypoglycaemia
Timepoint [5] 335273 0
This will be asked verbally 60/90/120/150/180 minutes post ingestion of MCT/placebo
Secondary outcome [6] 335315 0
working memory neurocognitive functioning
Timepoint [6] 335315 0
20 minutes prior to MCT/Placebo administration a 5 minute 'two back cognitive assessment is completed in the MRI for baseline
100- 105 minutes post administration a 5 minute cognitive testing 'two back' will be completed whilst participant is in MRI .

Eligibility
Key inclusion criteria
T1DM >1 year, HbA1c<9%
Minimum age
12 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
IQ<70 or attendance at a special educational setting, diagnosis of, or treatment for mental health or neurodevelopmental disorder, previous history of neurological disease trauma, history of diabetic ketoacidosis, contra-indication to MRI (metal implants or major dental work)

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)
Following enrolment and the collection of pre-study data, participants will be randomised, using a computer-generated randomisation schedule to one of two study groups (A or B). This schedule will be generated by an independent statistician using block randomisation to maintain balance between groups. Groups will differ in the order in which they receive the MCT and placebo mixtures over the 2 research days. Participants and all members of the study team will be blinded to study group allocation. The schedule will be provided to the RCH formula room (who will prepare the drinks. Sealed envelopes containing the allocation of each randomisation code will be provided to the investigator to use in case of emergency.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Only enough funding for a pilot trial at this point

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
24/12/2016
Date of last participant enrolment
Anticipated
1/09/2017
Actual
Date of last data collection
Anticipated
1/12/2017
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7933 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 15898 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 296353 0
Other
Name [1] 296353 0
Murdoch Childrens Research Institute
Country [1] 296353 0
Australia
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
50 Flemington Road, Parkville, Vic 3052
Country
Australia
Secondary sponsor category [1] 295285 0
None
Name [1] 295285 0
Address [1] 295285 0
Country [1] 295285 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297583 0
Royal Childrens Hospital HREC
Ethics committee address [1] 297583 0
Research Ethics and Governance
The Royal Children’s Hospital Melbourne
50 Flemington Road, Parkville, 3052
VIC AUS
Ethics committee country [1] 297583 0
Date submitted for ethics approval [1] 297583 0
01/11/2016
Approval date [1] 297583 0
19/12/2016
Ethics approval number [1] 297583 0
36183A

Summary
Brief summary
The aim of this study is to assess whether medium chain triglycerides (MCT) can protect the brains of adolescents with type1 diabetes mellitus (T1D) during hypoglycaemia.
Glucose is the dominant metabolic substrate for brain function. Hypoglycaemia is an inevitable consequence of insulin therapy in type 1 diabetes mellitus (T1D). Even with good control, children and adolescents with T1D spend up to one hour per day with blood glucose levels in the hypoglycaemic range. If untreated, hypoglycaemia can lead to impaired cognition, loss of consciousness and potentially death. Fear of the neurologic consequences of hypoglycaemia is one of the main impediments to optimal metabolic control in children with T1D. Thus there is an imperative for neuroprotective therapies that mitigate or prevent the effects of hypoglycaemia.
Using hyperinsulinaemic glucose clamp techniques and simultaneous neuroimaging we have previously investigated the effects of hypo- and hyperglycaemia on brain metabolism, neural networks and cognition in adolescents with T1D. Our studies found clinically important, novel, consistent and robust changes in regional brain perfusion, activation and metabolism during passage from euglycaemia to hypoglycaemia. These abnormalities in neuronal activity persist over hours despite return to euglycaemia. We now plan to exploit these novel findings and to study whether the observed changes can be mitigated or prevented by the prophylactic administration of MCT prior to hypoglycaemic challenge.
We will test the efficacy of MCT during clamp-induced hypoglycaemia in a randomised, cross-over placebo-controlled trial. The study population will be 10 adolescents aged 12-18years with Type 1 diabetes, recruited from the Diabetes Clinic at the Royal Children’s Hospital, Melbourne. Our primary outcome will be difference in cerebral perfusion as measured by arterial spin labelling – ASL) during hypoglycaemia induced following MCT as compared with placebo.. Our secondary outcomes will be differences between groups in, functional connectivity /activation in the default mode network (measured using blood oxygen level dependent [BOLD] signalling), brain metabolism (measured using BOLD signalling), frontal lobe biochemistry (measured spectroscopically) and cognitive function (measured on a working memory task). We hypothesize that the changes in all of these outcome measures during hypoglycaemia will be mitigated or prevented by prior oral MCT administration.
Our ultimate aim is to devise a simple oral therapy that can be taken by all children with T1D to protect the brain from hypoglycaemia. This will lead to improved neurologic outcomes and facilitate better overall metabolic control of their diabetes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74514 0
Prof Fergus Cameron
Address 74514 0
Royal Children's Hospital
50 Flemington Road, Parkville,
VIC, AUS 3052
Country 74514 0
Australia
Phone 74514 0
+6138345 5608
Fax 74514 0
Email 74514 0
fergus.cameron@rch.org.au
Contact person for public queries
Name 74515 0
Julia McCombe
Address 74515 0
MCRI Level 5, 50 Flemington Road, Parkville, VICTORIA, AUS 3052
Country 74515 0
Australia
Phone 74515 0
+61383416224
Fax 74515 0
Email 74515 0
julia.mccombe@mcri.edu.au
Contact person for scientific queries
Name 74516 0
Julia McCombe
Address 74516 0
MCRI Level 5, 50 Flemington Road, Parkville, Victoria Australia, 3052
Country 74516 0
Australia
Phone 74516 0
+61383416224
Fax 74516 0
Email 74516 0
julia.mccombe@mcri.edu.au

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

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