ANZCTR - Registration

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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

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]

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

Hypoglycaemia

Condition category

Condition code

Metabolic and Endocrine

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]

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]

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]

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]

Blood oxygen level dependent (BOLD) signal will be used to assess both metabolic activity and functional connectivity of the brain

Timepoint [1]

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]

Cogstate aggregate scores to assess neurocognitive function

Timepoint [2]

.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]

Magnetic resonance spectroscopy will assess aspects of higher neurocognitive function

Timepoint [3]

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]

Serum ketone levels will assess the degree of ketonemia generated

Timepoint [4]

This will be done at 15 minute intervals for 3 hours post administration of MCT/placebo using keytone strips

Secondary outcome [5]

Self reported symptoms of hypoglycaemia

Timepoint [5]

This will be asked verbally 60/90/120/150/180 minutes post ingestion of MCT/placebo

Secondary outcome [6]

working memory neurocognitive functioning

Timepoint [6]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Royal Childrens Hospital - Parkville

Recruitment postcode(s) [1]

3052 - Parkville

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Murdoch Childrens Research Institute

Address [1]

50 Flemington Road, Parkville, Vic 3052

Country [1]

Australia

Primary sponsor type

Other

Name

Murdoch Childrens Research Institute

Address

50 Flemington Road, Parkville, Vic 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Childrens Hospital HREC

Ethics committee address [1]

Research Ethics and Governance
The Royal Children’s Hospital Melbourne
50 Flemington Road, Parkville, 3052
VIC AUS

Ethics committee country [1]

Date submitted for ethics approval [1]

01/11/2016

Approval date [1]

19/12/2016

Ethics approval number [1]

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

Prof Fergus Cameron

Address

Royal Children's Hospital
50 Flemington Road, Parkville,
VIC, AUS 3052

Country

Australia

Phone

+6138345 5608

Fax

[email protected]

Contact person for public queries

Name

Julia McCombe

Address

MCRI Level 5, 50 Flemington Road, Parkville, VICTORIA, AUS 3052

Country

Australia

Phone

+61383416224

Fax

[email protected]

Contact person for scientific queries

Name

Julia McCombe

Address

MCRI Level 5, 50 Flemington Road, Parkville, Victoria Australia, 3052

Country

Australia

Phone

+61383416224

Fax

[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.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically