Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000176066
Ethics application status
Approved
Date submitted
19/02/2010
Date registered
25/02/2010
Date last updated
10/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
What is the minimum amount of folic acid that improves blood vessel function in children with type 1 diabetes?
Scientific title
What is the minimum dose of folic acid that improves vascular health in children with type 1 diabetes?
Secondary ID [1] 1282 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 256533 0
Endothelial dysfunction 256534 0
Condition category
Condition code
Metabolic and Endocrine 256704 256704 0 0
Diabetes
Cardiovascular 256705 256705 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised double blind crossover placebo controlled trial. Intervention consists of folic acid, in one of the three doses available (0.5mg, 2mg or 5mg), as a single dose only (10ml), administered orally, in a random order. The duration between interventions is 4 weeks.
Intervention code [1] 255811 0
Prevention
Intervention code [2] 256045 0
Treatment: Drugs
Comparator / control treatment
Single 10ml dose of water, for oral administration.
Control group
Placebo

Outcomes
Primary outcome [1] 257591 0
Change in endothelial function measured by flow mediated dilatation (FMD)
Timepoint [1] 257591 0
2 hours after folic acid in one of the three available doses or placebo, in random order, at 4 visits 4 weeks apart
Secondary outcome [1] 262855 0
Nil
Timepoint [1] 262855 0
Nil

Eligibility
Key inclusion criteria
Type 1 diabetes of longer than 1 year duration (attending the Diabetes clinic at Women's and Children's Hospital, Adelaide)
Minimum age
10 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of smoking or serum cotinine level >28 nmol/l;
Coeliac disease, screened by transglutaminase immunoglobulin A (IgA);
Treatment with statins or angiotensin converting enzyme inhibitors;
Vitamin supplementation;
Vitamin B12 deficiency;
Intercurrent illness or ketosis at the time of the study.

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)
After recruitment, subjects will be assigned a unique identifying number. Randomisation with this identifying number will be performed by the Pharmacy Department at Women's and Children's Hospital, Adelaide.
Each subject will receive a single dose of folic acid (0.8mg, 2mg or 5mg) or placebo every month. Both folic acid and placebo will be prepared in identical liquid preparation and delivered from an amber coloured bottle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be using a computerised sequence generator that creates random balanced permutations of treatments for subjects who are to receive all of the treatments in a random order.

Reference:
www.randomization.com
Author: Gerard E. Dallal
Last modified: 16 July 2008
Access date: 29 January 2010
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
2/03/2010
Actual
20/03/2010
Date of last participant enrolment
Anticipated
2/10/2010
Actual
2/10/2010
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256304 0
Hospital
Name [1] 256304 0
Women's and Children's Hospital Foundation
Country [1] 256304 0
Australia
Primary sponsor type
Individual
Name
Dr Alexia Pena
Address
Endocrinology and Diabetes Centre
Women's and Children's Hospital
72 King William Rd
North Adelaide SA 5006
Country
Australia
Secondary sponsor category [1] 251624 0
Hospital
Name [1] 251624 0
Women's and Children's Hospital
Address [1] 251624 0
72 King William Rd
North Adelaide SA 5006
Country [1] 251624 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258388 0
Children, Youth and Women's Health Service Human Research Ethics Committee
Ethics committee address [1] 258388 0
2nd level Samuel Way Building
Women's and Children's Hospital
72 King William Road
North Adelaide, SA 5006
Ethics committee country [1] 258388 0
Australia
Date submitted for ethics approval [1] 258388 0
16/11/2009
Approval date [1] 258388 0
10/02/2010
Ethics approval number [1] 258388 0
12/12/2232

Summary
Brief summary
Children with type 1 diabetes have detectable arterial endothelial dysfunction and arterial intima-media thickening as first markers of accelerated atherosclerosis. They can be reliably measured to test the effectiveness of early intervention strategies. Folic acid supplementation significantly reduces the risk of stroke in adults, with most benefit in primary prevention. We have demonstrated that folic acid supplementation 5 mg daily rapidly normalizes endothelial function in children with type 1 diabetes, independent of homocysteine lowering. However there are no dose response studies of the benefit of folic acid to determine the minimum effective dose. This is relevant as while high dose folic acid does not have short term adverse effects, recent epidemiological data questions its long term safety in individuals with established vascular or early neoplastic disease. Determining the minimum dose of folic acid that improves endothelial function and the effect of endothelial nitric oxide synthase polymorphisms on the response to folic acid, will also inform future intervention trials for accelerated atherosclerosis in this age group.
Trial website
Trial related presentations / publications
- Pena AS, Maftei O, Gent R, Piotto L, Gaskin K, Dowling K, Couper J. (2011) The effects of folate supplementation on endothelial function in children with type 1 diabetes are abolished after introduction of folate fortification, XXII Annual Meeting of the Latin American Society of Pediatric Endocrinology, Cartagena, Colombia, September 7-10, Abstract P48, p.114.
- Pena AS, Maftei O, Dowling K, Gent R et al. "Folate Fortification and Supplementation Do Not Provide Vascular Health Benefits in Type 1 Diabetes" (2013) Journal of Pediatrics Vol. 163, Issue 1, Pages 255-260
Public notes

Contacts
Principal investigator
Name 30697 0
Dr Alexia Pena
Address 30697 0
Endocrinology and Diabetes Centre
Women's and Children's Hospital
72 King William Rd
North Adelaide SA 5006
Country 30697 0
Australia
Phone 30697 0
+61 8 81618134
Fax 30697 0
Email 30697 0
[email protected]
Contact person for public queries
Name 13944 0
Dr Oana Maftei
Address 13944 0
Endocrinology and Diabetes Centre
Women's and Children's Hospital
72 King William Rd
North Adelaide SA 5006
Country 13944 0
Australia
Phone 13944 0
+61 8 81618134
Fax 13944 0
Email 13944 0
[email protected]
Contact person for scientific queries
Name 4872 0
Dr Alexia Pena
Address 4872 0
Endocrinology and Diabetes Centre
Women's and Children's Hospital
72 King William Rd
North Adelaide SA 5006
Country 4872 0
Australia
Phone 4872 0
+61 8 81618134
Fax 4872 0
Email 4872 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.