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Trial registered on ANZCTR


Registration number
ACTRN12620000655943
Ethics application status
Approved
Date submitted
4/05/2020
Date registered
5/06/2020
Date last updated
5/06/2020
Date data sharing statement initially provided
5/06/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Relationship between vitamin C deficiency and frailty in acutely hospitalized patients
Scientific title
Association between vitamin C deficiency and frailty in elderly patients aged 75 and above admitted in the acute medical wards
Secondary ID [1] 301181 0
Nil known
Universal Trial Number (UTN)
N/A
Trial acronym
N/A
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Vitamin C deficiency
317330 0
Frailty 317331 0
Condition category
Condition code
Diet and Nutrition 315439 315439 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients will be approached by the research team members in order to provide consent for blood test sample to measure vitamin C; an information sheet will be provided explaining the trial, its aims and the possibility of withdrawing at any time. There will be only a once off encounter with the patient permitting full assessment of frailty and measure confounding factors. Patients, if deemed to have capacity to consent, or guardians of patients, will be allowed to make an informed consent.
Intervention code [1] 317493 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323689 0
We expect to determine the prevalence of vitamin C deficiency amongst frail elderly inpatients, assessed by morning serum measurement of vitamin C level
Timepoint [1] 323689 0
At the first encounter with an eligible consenting patient (once off)
Primary outcome [2] 323691 0
To determine whether frail patients who are vitamin C deficient have longer length of stay in hospital
Timepoint [2] 323691 0
Single occasion in each participant- case notes follow up
Primary outcome [3] 323913 0
Determine if frail patients with vitamin C deficiency have higher mortality
Timepoint [3] 323913 0
Single occasion- follow-up of case notes
Secondary outcome [1] 383321 0
Determine if frail patients with vitamin C deficiency have more complications during admission
Timepoint [1] 383321 0
Once-off- review of case notes

Eligibility
Key inclusion criteria
A member of the research team will approach the participants and a written informed consent will be obtained from the participants. In case of cognitive impairment, the decision regarding participants’ capacity will be made from their mini mental state examination (MMSE) scores. For this study, we will only approach those patients > 75 yo referred by ED to General Medicnie acute admission with a score of 19 to 24 on the MMSE. An MMSE score of 19-24 indicates mild cognitive impairment, but given the low complexity of this project, patients would still be expected to have capacity and consent for themselves. Patients with MMSE below 19 will be excluded on the basis that they will be unable to provide informed consent for themselves. We will adhere to recommendations from Black et al (9) regarding assessment of verbal, behavioural, and emotional cues expressing comprehension and assent
Minimum age
75 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Vitamin C treatment/supplementation
Palliative patients
Lack of valid consent
Reluctance to participate or hesitancy

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The sample size was calculated on the basis of logistic regression analysis (outcome variable vitamin C replete equal 0 and vitamin C deficient equals 1), for which we only need the following co-variates:
Age (in years)
Sex
Charlson index
MUST (Malnutrition universal screening tool) score
Determination of sample size for logistic regression studies is a complex problem, so applying the guidelines suggested above and based on a recent study7, which has suggested that two-thirds of older hospitalised patients have vitamin C deficiency, assuming that 25% of older will be vitamin C replete and the number of co-variates equal 4 (age, sex, Charlson index and MUST score) a minimum of 160 will be required.
N = 10 X 4/0.25 equal 160
We will adjust for potential confounders by including age, sex, Charlson index and MUST score as co-variates in the logistic regression analyses of the ‘primary’ and ‘secondary’ outcomes. As there will be minimal involvement of patients with no collection of data for follow-up visits, the rate of withdrawal is expected to be negligible; should a patient choose to withdraw from the study then the associated data will be deleted and a replacement participant will be sought.

Recruitment
Recruitment status
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)
SA
Recruitment hospital [1] 16601 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 30198 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 305638 0
Hospital
Name [1] 305638 0
Flinders Medical Centre, SALHN
Address [1] 305638 0
Flinders Drive, Bedford Park 5042 SA
Country [1] 305638 0
Australia
Primary sponsor type
Hospital
Name
Flinders Medical Centre
Address
Flinders Drive, Bedford Park, 5042, SA
Country
Australia
Secondary sponsor category [1] 306038 0
None
Name [1] 306038 0
Address [1] 306038 0
Country [1] 306038 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305920 0
The Southern Adelaide Clinical Human Research Ethics Committee (SAC HREC EC00188)
Ethics committee address [1] 305920 0
Flinders Drive, Bedford Park 5042 SA
Ethics committee country [1] 305920 0
Australia
Date submitted for ethics approval [1] 305920 0
22/02/2019
Approval date [1] 305920 0
09/08/2019
Ethics approval number [1] 305920 0
OFR Number: 64.19 HREC reference number: HREC/19/SAC/72

Summary
Brief summary
We hypothesize that acutely hospitalized frail patients may have vitamin C deficiency and this could be associated with poorer outcomes during inpatient stay (longer LOS, higher mortality, complications etc). This study aims to look prospectively for an association between vitamin C deficiency and frailty, which hasn't been evaluated in the past and if this is demonstarted,this can pave the way to future research to determine new treatment options for frail patients.



Trial website
Trial related presentations / publications
Public notes
Literature review:
The prevalence of frailty in acutely hospitalised older patients can be up to 48% (1) and frail patients have poor clinical outcomes measured in terms of increased mortality, poor health related quality of life (HRQoL) and higher number of unplanned readmissions(.2,3). Studies suggest that oxidative stress may be associated with frailty and preliminary evidence points to lower anti-oxidant parameters in frail patients.(4) Vitamin C acts as a powerful anti-oxidant but whether vitamin C deficiency is associated with frailty has not yet been established.(5). Although research has indicated that low intake of vitamin C may increase risk of frailty, limited studies have verified this hypothesis by measuring plasma vitamin C levels, which is regarded as a more accurate assessment of vitamin C status.(6 0Previous studies have also suggested that other micronutrient deficiency (especially vitamin D and vitamin B12 deficiency) may be associated with frailty but the relationship between biochemical vitamin C deficiency and frailty is unclear.(6) A recent study has also suggested that two-third of hospitalised patients may have biochemical vitamin C deficiency.(7) This research will therefore explore the relationship between plasma vitamin C levels and frailty in acutely hospitalised older general medical patients and will determine whether frail patients have a higher prevalence of vitamin C deficiency. This study will also determine whether frail patients who are vitamin C deficient have poorer clinical outcomes as compared to those who are vitamin C replete.

References:
1. Ibrahim K, Howson FFA, Culliford DJ, Sayer AA, Roberts HC. The
feasibility of assessing frailty and sarcopenia in hospitalised older people: a comparison of commonly used tools. BMC Geriatr 2019;19(1):42.
2. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013;381(9868):752-62.
3. Morley JE, Vellas B, van Kan GA, Anker SD, Bauer JM, Bernabei R et al. Frailty consensus: a call to action. J Am Med Dir Assoc 2013;14(6):392-7.
4. Soysal P, Ahmet TS, Andre FC, Fernandes BS, Solmi M, Schofield P et al. Oxidative stress and frailty: A systematic review and synthesis of the best evidence. Maturitas 2017;99: 66-72.
5. Hemila H, Chalker E. Vitamin C can shorten the length of stay in the ICU: A meta-analysis. Nutrients 2019; 11(4):pii:E708.
6. Semba RD, Bartali B, Zhou J, Blaum C, Ko CW, Fried LP. Low serum micronutrient concentrations predict frailty among older women living in the community. J Gerontol A Biol Sci Med Sci 2006;61(6):594-9.
7. Sharma Y, Miller M, Shahi R, Doyle A, Horwood C, Hakendorf P et al. Vitamin C deficiency in Australian hospitalized patients: an observational study. Intern Med J 2018

Contacts
Principal investigator
Name 102066 0
Dr Yogesh Sharma
Address 102066 0
Flinders Medical Centre, Flinders Drive, Bedford Park, 5042 SA
Country 102066 0
Australia
Phone 102066 0
+61 882045511
Fax 102066 0
Email 102066 0
Yogesh.Sharma@sa.gov.au
Contact person for public queries
Name 102067 0
Dr Alexandra Popescu
Address 102067 0
Flinders Medical Centre, Flinders Drive, Bedford Park, 5042 SA
Country 102067 0
Australia
Phone 102067 0
+61 882045511
Fax 102067 0
Email 102067 0
Alexandra.Popescu@sa.gov.au
Contact person for scientific queries
Name 102068 0
Dr Alexandra Popescu
Address 102068 0
Flinders Medical Centre, Flinders Drive, Bedford Park, 5042 SA
Country 102068 0
Australia
Phone 102068 0
+61 882045511
Fax 102068 0
Email 102068 0
Alexandra.Popescu@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We do not have any plans to share the data and any follow-up research will need an ethical approval
What supporting documents are/will be available?
No other documents available
Summary results
No Results