Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000524796
Ethics application status
Approved
Date submitted
7/05/2013
Date registered
13/05/2013
Date last updated
13/05/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
The interactive impact of psychological stress and malnutrition on genome stability and telomere integrity in Carers (Telomeres, stress and nutrition).
Scientific title
In primary carers of Alzheimer’s Disease patients does the interactive impact of chronic stress and malnourishment increase the risk of telomere, genome and epigenome instability, compared with non-carers.
Secondary ID [1] 282463 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
DNA damage and telomere instability 289076 0
The molecular impact of psychological stress 289077 0
Association of nutritional biomarkers with stress and DNA stability. 289078 0
Condition category
Condition code
Diet and Nutrition 289418 289418 0 0
Other diet and nutrition disorders
Other 289435 289435 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
No intervention. Cross sectional, case control study.
(a) Biomarkers of DNA stability and nutritional status will be determined in Carers of partners/family members diagnosed with Alzheimer's Disease.
(b) Biomarkers of telomere, genome and epigenome stability will be observed in association with physiological measures (plasma and saliva) of stress hormones and micronutrients status. In addition questionnaire measures will be determined for perceived stress, healthy lifestyle behaviours and cognitive function.
(c) Carers who meet the inclusion criteria, whose partner has been diagnosed with AD at least one year prior will be included.
(d) The 'case' group comprises primary Carers of a person diagnosed with AD at least 1 year prior to sample collection. The 'control' group comprises age and gender matched non-carers.
Questionnaires will be posted out to participants prior to their single visit to the Clinic, together with a saliva collection kit. Participants will be asked to complete the questionnaires (approximately 1 hour) in the week prior to their Clinic visit. The saliva test will need to be self-administered the night prior to their Clinic appointment, and brought into their appointment. The saliva test involves a cotton swab in the mouth for 3 minutes. Participants will be required to attend a single Clinic visit only which is estimated to be approximately 1 hour in duration. At this visit fasted blood samples will be taken, breakfast will be provided, and the Mini Mental State Examination (MMSE) will be administered in person by a member of the research team.
Intervention code [1] 287109 0
Not applicable
Comparator / control treatment
Comparing psychological & physiological parameters between carers and age and gender matched non-carers.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289525 0
Telomere length (TL) will be determined by flow cytometry, in primary leukocytes isolated from whole blood by gradient separation. TL will be measured in viable cells at G1 stage of the cell cycle.
Timepoint [1] 289525 0
Leukocytes will be isolated immediately upon blood collection, and viably frozen prior to TL measures being conducted.
Secondary outcome [1] 302673 0
Biomarkers of DNA damage will be determined using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay which allows assessment of micronuclei, nucleoplasmic bridges, nuclear buds, fused or circular nuclei, damaged mononuclear cells, as well as markers of cytostasis (nuclear division index, apoptosis, necrosis).
Timepoint [1] 302673 0
Leukocytes will be isolated immediately upon blood collection and fresh 72-hour cultures established for the CBMN-cyt assay.
Secondary outcome [2] 302674 0
Physiological measures: Blood samples will be centrifuged and aliquotted for determination of plasma concentrations of micronutrients and related metabolites, plasma and salivary cortisol, plasma adrenaline (Ad) and noradrenaline (NAd) by the accredited medical pathology laboratory at the Institute of Veterinary & Medical Sciences (IMVS), Adelaide, and the Royal Prince Alfred Hospital (Ad and NAd only).
Timepoint [2] 302674 0
Fresh blood samples will be centrifuged immediately, aliquotted and collected by IMVS for analysis, or stored appropriately in -80 degree storage prior to shipping/analysis.
Secondary outcome [3] 302675 0
Epigenome stability will be determined by analysis of DNA methylation status.
Timepoint [3] 302675 0
DNA isolated from leukocytes harvested immediately following blood collection.

Eligibility
Key inclusion criteria
Inclusion criteria - Carers: Primary carer of a person diagnosed with Alzheimer’s Disease (AD); =1 year since partner’s AD diagnosis; Male or female; Aged 65-90 years

Inclusion criteria - Control Group: Male or female; Aged 65-90 years.
Minimum age
65 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria - Carers: Diagnosed with a neurodegenerative condition, cognitive impairment or chronic illness requiring ongoing medical treatment; Undergoing chemotherapy/radiotherapy for cancer treatment; Supplementing with above RDI intakes of micronutrients associated with genome maintenance (eg. folate, vitamin B12); Consuming more than 3 standard alcoholic drinks/day; Smoker (5 or more cigarettes/day).

Exclusion criteria - Control Group: Carer for a family member with a serious chronic illness/condition, living in the home; Diagnosed with a neurodegenerative condition, cognitive impairment or chronic illness requiring ongoing medical treatment; Undergoing chemotherapy/radiotherapy for cancer treatment; Supplementing with above RDI intakes of micronutrients associated with genome maintenance (eg. folate, vitamin B12); Consuming more than 3 standard alcoholic drinks/day; Smoker (5 or more cigarettes/day).

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
100 participants will be recruited; 50 primary carers of partners diagnosed with AD, and 50 age/gender matched non carers (controls). Where possible, we aim to recruit 25 males and 25 females.
Power analysis - Telomere length: With n = 50 participants per group we can detect difference in telomere length of 1.7%, with 99% power, with significance at p = 0.05. Telomere shortening through natural ageing processes occurs at roughly 8% per decade, thus 1.7% would indicate approximately 2 years difference in ageing between groups.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 287245 0
Government body
Name [1] 287245 0
Commonwealth Scientific and Industrial Research Organisation (CSIRO) Preventative Health Flagship
Country [1] 287245 0
Australia
Primary sponsor type
Government body
Name
Commonwealth Scientific and Industrial Research Organisation (CSIRO) Preventative Health Flagship
Address
Gate 13 Kintore Avenue
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 285996 0
None
Name [1] 285996 0
Address [1] 285996 0
Country [1] 285996 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Aim: The aim of this pilot study is to examine the interactive effects of psychological stress and malnutrition on DNA damage and epigenome biomarkers in a long term chronically-stressed cohort.

Hypotheses: (i) Stress hormones induce specific types of DNA damage at the gene sequence, epigenome and chromosome level, including compromised telomere length and integrity; (ii) Susceptibility to DNA damage by the stress hormone cortisol is increased when dietary B vitamin methyl donors (folate, vitamin B12, choline) are deficient; (iii) Telomere length is inversely associated with perceived and actual stress, and this relationship is strengthened with increased chronicity of stress exposure.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39862 0
Dr Caroline Bull
Address 39862 0
CSIRO Animal, Food and Health Sciences
Gate 13 Kintore Avenue
Adelaide SA 5000
Country 39862 0
Australia
Phone 39862 0
+618 8 3038931
Fax 39862 0
Email 39862 0
[email protected]
Contact person for public queries
Name 39863 0
Caroline Bull
Address 39863 0
CSIRO Animal, Food and Health Sciences
Gate 13 Kintore Avenue
Adelaide SA 5000
Country 39863 0
Australia
Phone 39863 0
+61 8 83038931
Fax 39863 0
Email 39863 0
[email protected]
Contact person for scientific queries
Name 39864 0
Caroline Bull
Address 39864 0
CSIRO Animal, Food and Health Sciences
Gate 13 Kintore Avenue
Adelaide SA 5000
Country 39864 0
Australia
Phone 39864 0
+61 8 83038931
Fax 39864 0
Email 39864 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
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