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Trial registered on ANZCTR


Registration number
ACTRN12611000403932
Ethics application status
Approved
Date submitted
11/04/2011
Date registered
18/04/2011
Date last updated
28/04/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Dietary supplementation and symptoms of sub-health
Scientific title
Characterization of differential amino acid homeostasis subgroups in healthy adults reporting symptoms of sub-health: a basis for determining specific amino acid requirements and the efficacy of an amino acid supplement in improving symptoms of sub-health
Secondary ID [1] 259963 0
Nil
Universal Trial Number (UTN)
U1111-1119-7730
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sub-health 265593 0
Condition category
Condition code
Alternative and Complementary Medicine 265739 265739 0 0
Other alternative and complementary medicine
Other 265740 265740 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The first stage of the study has been designed in order to provide evidence that phenotypic subsets exist within the sub-health population which may indicate differential nutritional requirements. Initially 400 participants will be recruited to allow for sub-grouping based upon differential amino acid homeostasis. From each subgroup 20 individuals will be asked to participate in the amino acid supplement trial. It is envisaged that 100-120 individuals will participate in the second stage however this will be depend upon the number of sub-groups identified after stage 1. Participants from stage 1 will be randomly chosen for inclusion in stage 2, although age- and sex-matching will be undertaken.

Arm 1 (project involves two stages however Arm 1 does not involve a “treatment”) - Metabolic Profiling: Healthy adults reporting symptoms of sub-health will be asked to complete a medical history questionnaire (medical history, age, sex, ethnicity, medications, whether pregnant) in part to determine eligibility. If eligible, participants will be asked to complete a questionnaire regarding 86 symptoms including fatigue, mood, immune dysfunction, neurocognition etc. Complete Chalder Fatigue Scale questionnaire (11 questions). List current medications/supplements. They will be asked to collect at home a fasted first-morning (after 5am) urine sample. Fasted indicates participant cannot eat after 10pm the night before collection and should only drink a small amount of water if necessary. Urine samples will be assessed for amino acid content.

Arm 2 – Amino Acid Supplement Trial: Individuals randomly chosen from Arm 1 of the study will be asked to take 20g of an amino acid supplement once daily for 30 days. The supplement, in the form of a powder may be mixed in water. The supplement, Fatigue Reviva, is a food supplement material and is produced by TOP Nutrition Pty Ltd. The morning following the final day of the trial participants will again be required to complete the symptom and fatigue questionnaires; provide a urine sample; answer a number of open-ended questions regarding experience of using the supplement and list medications/supplements.
Intervention code [1] 264377 0
Early detection / Screening
Intervention code [2] 264378 0
Treatment: Other
Comparator / control treatment
The study will be uncontrolled. The intervention will be applied to all subjects taking part in Arm 2 of the study. The first stage of the study has been designed in order to provide evidence that phenotypic subsets exist within the sub-health population which may indicate differential nutritional requirements. The second phase of the project will then be carried out in order to determine whether the amino acid supplement shows evidence of efficacy in the different phenotypic subtypes identified during Arm 1. It is expected, based upon our previous research findings, that there will be a significant difference in the proportion of those from each “subtype” group who respond positively to amino acid supplementation. It is envisaged that a phenotypic specific response will be seen. The research project seeks to gather evidence to determine whether various population phenotypic groups may have differential requirements for amino acid supplementation. Hence the responses will be compared between the phenotypic groups.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 266496 0
Primary Outcome 1: mean general health questionnaire scores (questionnaire developed by our laboratory and used over a number of years; uses a 5 point Likert scale; includes 86 questions regarding both physical and psychological health).
Timepoint [1] 266496 0
Timepoint: immediately following 30 days of amino acid supplementation.
Primary outcome [2] 266497 0
Primary Outcome 2: amino acid profiling based upon multivariate statistical techniques (urinary amino acid levels determined using GC-MS; statistical analysis performed on both concentration and relative abundance data).
Timepoint [2] 266497 0
Timepoint: pre- and immediately post-amino acid supplementation.
Secondary outcome [1] 273895 0
Secondary Outcome 1: mean Chalder Fatigue Scale Score.
Timepoint [1] 273895 0
Timepoint: immediately following 30 days of amino acid supplementation.

Eligibility
Key inclusion criteria
Adults suffering from symptoms of sub-health (tiredness, fatigue, lack of energy, sub-optimal levels of performance).

Free from significant medical/psychiatric conditions.

Must not be pregnant.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Previously diagnosed with a significant medical or psychiatric condition.

Pregnancy

Intellectual disability

Less than 18 years of age

Dependent on significant medical care

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Allocation to intervention: we have indicated that the trial is nonrandomised. The project involves two arms. In Arm 1 participants will provide a urine sample which will be analysed for amino acid content. This information will then be used to subtype the participants based upon their amino acid profiles. It is envisaged from our past research that 5 or 6 subgroups will be identified. In the second arm of the study 20 individuals will be randomly chosen to represent each subgroup from the larger initial cohort. Individuals will be selected to go onto the second arm of the study using a simple randomisation technique, a randomisation table created by computer software. In the second arm of the study all participants will be given the same amino acid supplement, in the same quantity and for the same duration. As such the participants receiving the intervention will not be randomised to different interventions.

Target sample size: we have indicated 120 as the target sample size for the intervention (amino acid supplement) phase of the project. The target sample size for Arm 1 of the study which does not involve an intervention/treatment is 400.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
NSW,QLD,WA,VIC
Recruitment postcode(s) [1] 3910 0
2258
Recruitment postcode(s) [2] 3911 0
2308

Funding & Sponsors
Funding source category [1] 264848 0
Commercial sector/Industry
Name [1] 264848 0
DRbiolab
Address [1] 264848 0
Dunstan Roberts Laboratory, Room LS4.10, Life Sciences Building, The University of Newcastle, University Drive, Callaghan, NSW, 2308
Country [1] 264848 0
Australia
Funding source category [2] 264850 0
Commercial sector/Industry
Name [2] 264850 0
Top Nutrition Pty Ltd
Address [2] 264850 0
PO Box 611, Kotara, NSW, 2289
Country [2] 264850 0
Australia
Primary sponsor type
Individual
Name
Associate Professor R Hugh Dunstan
Address
Head of School, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW, 2308
Country
Australia
Secondary sponsor category [1] 263947 0
Individual
Name [1] 263947 0
Professor Tim Roberts
Address [1] 263947 0
Director Tom Farrell Institute for the Environment, University of Newcastle, University Drive, Callaghan, NSW, 2308
Country [1] 263947 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266813 0
The University of Newcastle Human Research Ethics Committee (EC00144)
Ethics committee address [1] 266813 0
The University of Newcastle, Callaghan, NSW, 2308.
Ethics committee country [1] 266813 0
Australia
Date submitted for ethics approval [1] 266813 0
23/11/2010
Approval date [1] 266813 0
04/08/2011
Ethics approval number [1] 266813 0
H-2010-1313

Summary
Brief summary
Individually and as the constituents of proteins, amino acids perform numerous and often essential functions. The current researchers have previously demonstrated clearly defined population subgroups based upon urinary amino acid profiles in chronic fatigue and pain patients, each group with specific nutritional requirements for amino acids. The same subgroups were also identified in healthy individuals with profiles differing from the patient groups only in the degree of excess or depletion of amino acids. The current project aims to determine whether distinct subgroups can be identified in healthy individuals reporting sub-health on the basis of urinary amino acid patterns. Sub-health is typically seen as a reduction in energy levels, change in sleeping patterns, increased incidence of viral infections and a loss of vitality with no defined disease being diagnosed. It can be defined as a chronic condition of deteriorated physiological function between health and illness. The project also aims to assess the ability of amino acid supplementation to improve the general well-being of individuals experiencing sub-health based upon membership of the subgroups identified in stage one.

The current researchers have developed a nutritional formulation to alleviate fatigue containing a complex range of amino acids. The study will trial the amino acid supplement in subgroups of healthy individuals reporting sub-health. The study will involve a large group of adults reporting fatigue and sub-health but who are free from any significant medical or mental illness. Prior to supplementation all participants will be required to provide a urine sample and to complete general health and fatigue questionnaires. Urinary amino acid excretion patterns will be assessed with the aim of identifying subgroups based upon differential amino acid homeostasis. Once the subgroups have been differentiated, smaller groups of twenty individuals from each subgroup will trial the supplement for 30 days. At the completion of the trial participants will provide another urine sample and again complete the general health and fatigue questionnaires. General health, fatigue and urinary amino acid levels will be analysed to determine whether supplementation can bring about changes at both a symptom and biological level. It is believed that participants will derive significant benefits such as reduced fatigue but that the response to supplementation will be influenced by amino acid profile subgroup membership. This study will determine whether readily identifiable amino acid profile subgroups exist, each with specific amino acid requirements, allowing for the development of more effective dietary supplements in the future.

The project’s hypotheses are as follows:
1. It is possible to identify major subtypes of amino acid homeostasis in a population.
2. Amino acid supplementation is capable of alleviating symptoms of sub-health and the symptoms and degree of alleviation will be determined by membership of subgroups based upon amino acid homeostasis.
Trial website
Trial related presentations / publications
Dunstan RH, Sparkes DL, Macdonald MM, De Jonge XJ, Dascombe BJ, Gottfries J, et al., 'Diverse characteristics of the urinary excretion of amino acids in humans and the use of amino acid supplementation to reduce fatigue and sub-health in adults.', Nutr J, 16 19 (2017)

Dunstan RH, Sparkes DL, Roberts TK, Dascombe BJ, 'Preliminary Evaluations of a Complex Amino Acid Supplement, Fatigue Reviva, to Reduce Fatigue in a Group of Professional Male Athletes and a Group of Males Recruited from the General Public', Food and Nutrition Sciences, 5 231-235 (2014)

Dunstan RH, Sparkes DL, Roberts TK, Crompton MJ, Gottfries J, Dascombe BJ, 'Development of a complex amino acid supplement, Fatigue Reviva (TM), for oral ingestion: initial evaluations of product concept and impact on symptoms of sub-health in a group of males', NUTRITION JOURNAL, 12 (2013)
Public notes

Contacts
Principal investigator
Name 32464 0
Prof R Hugh Dunstan
Address 32464 0
Prof Hugh Dunstan
School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW, 2308
Country 32464 0
Australia
Phone 32464 0
61 02 4921 5687
Fax 32464 0
Email 32464 0
hugh.dunstan@newcastle.edu.au
Contact person for public queries
Name 15711 0
Prof Prof R Hugh Dunstan
Address 15711 0
School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW, 2308
Country 15711 0
Australia
Phone 15711 0
62 2 4921 5687
Fax 15711 0
+61 2 49215361
Email 15711 0
hugh.dunstan@newcastle.edu.au
Contact person for scientific queries
Name 6639 0
Prof Prof R Hugh Dunstan
Address 6639 0
School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW, 2308
Country 6639 0
Australia
Phone 6639 0
61 2 4921 5687
Fax 6639 0
+61 2 49215361
Email 6639 0
hugh.dunstan@newcastle.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary