Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000401853
Ethics application status
Approved
Date submitted
28/01/2021
Date registered
12/04/2021
Date last updated
12/04/2021
Date data sharing statement initially provided
12/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating probiotics for chronic fatigue in the Using Probiotics to Lessen the Impact of Fatigue in Teens (UPLIFT) Pilot Study
Scientific title
Investigating probiotics for chronic fatigue in the Using Probiotics to Lessen the Impact of Fatigue in Teens (UPLIFT) Pilot Study: A randomised, double blind, placebo controlled trial
Secondary ID [1] 303268 0
None
Universal Trial Number (UTN)
U1111-1264-2644
Trial acronym
UPLIFT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Fatigue Syndrome 320473 0
Condition category
Condition code
Other 318357 318357 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
Participants who are randomly assigned to the intervention group will receive capsules containing both the probiotics Lactobacillus rhamnosus HN001 (6X109 colony forming units) and Bifidobacterium animalis HN019 ((9×109 cfu) in the same capsule.

Participants will be instructed to take one single capsule a day for a period of 10 weeks.

Adherence will be assessed by asking participants to enter the number of remaining capsules they have in the bottle at the post-intervention data collection phase.
Intervention code [1] 319580 0
Treatment: Other
Comparator / control treatment
Approximately half the participants will be assigned to receive placebo capsules containing corn-derived maltodextrin. These capsules will be identical in taste, smell and appearance to the intervention capsules.
Participants will be instructed to take one capsule per day for 10 weeks.
Adherence will be assessed by asking participants to enter the number of remaining capsules they have in the bottle at the post-intervention data collection phase.
Control group
Placebo

Outcomes
Primary outcome [1] 326324 0
Mood and Feelings Questionnaire – Short Version (SMFQ) for young people. The short version of the MFQ is a 13-item questionnaire that asks young people about recent mood. Scores range from 0-26 with higher scores indicating higher levels of emotional difficulties.
Timepoint [1] 326324 0
SMFQ scores will be measured at baseline and following a 10 week intervention period, with the primary time point of interest being scores post the 10 week intervention period.
Primary outcome [2] 326325 0
Gastrointestinal symptoms: a brief questionnaire which assess the frequency and severity of gastrointestinal symptoms. Participants rate each of 5 symptoms for frequency and then severity thus answering 10 questions in total.
Timepoint [2] 326325 0
Gastrointestinal symptoms will be measured at baseline and following a 10 week intervention period, with the primary time point of interest being scores post the 10 week intervention period.
Primary outcome [3] 326326 0
Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL MDF) self-report for young people. This is an 18 item questionnaire that asks young people aged 13-18 years about symptoms of fatigue in three areas: General Fatigue, Sleep/Rest Fatigue and Cognitive Fatigue. Each subscale contains six questions. All subscales will be assessed as a composite primary outcome.
Timepoint [3] 326326 0
PedsQL MDF scores will be measured at baseline and following a 10 week intervention period, with the primary time point of interest being scores post the 10 week intervention period.
Secondary outcome [1] 391067 0
This is a primary outcome measure. State Trait Anxiety Inventory – six item (STAI-6): The STAI6 is a short six item version of the longer State Trait Anxiety Inventory used to assess symptoms of anxiety in the young participants.
Timepoint [1] 391067 0
STAI-6 scores will be measured at baseline and following a 10 week intervention period.
Secondary outcome [2] 392521 0
This is a primary outcome measure. Perceived Stress Scale: Parents/caregivers will complete the Perceived Stress Scale to rate their own levels of stress. The PSS is a 10 item questionnaire that asks people to rate how often in the preceding month they have felt stressed.
Timepoint [2] 392521 0
Perceived stress scores will be measured at baseline and following the 10 week intervention period.
Secondary outcome [3] 392522 0
This is a primary outcome measure. Mood and Feelings Questionnaire – Short version Parent Form: Like the SMFQ self-report for young people, the parent-form asks parents to rate their child’s recent mood. The 13-item scale gives scores ranging from 0-26 with higher scores indicating increasing emotional difficulties.
Timepoint [3] 392522 0
MFQ scores will be measured at baseline and following the 10 week intervention period.
Secondary outcome [4] 392523 0
This is a primary outcome measure. Parent rated Pediatric Quality of Life Multidimensional Fatigue Scale- Teen: Similar to the self-report version, the parent report version of the Pediatric Quality of life Inventory Multidimensional Fatigue Scale is an 18 item questionnaire that asks parents to report about their young person’s level of general fatigue, sleep/rest and cognitive fatigue. All subscales will be assessed as a composite primary outcome
Timepoint [4] 392523 0
Parent rated PedsQL scores will be measured at baseline and following the 10 week intervention period.
Secondary outcome [5] 392524 0
This is a primary outcome measure. Parent rated post-exertional malaise: Similar to the questions completed by young people, parents will be asked to rate the frequency of five post-exertional malaise symptoms in their children.
Timepoint [5] 392524 0
Parent rated post-exertion malaise will be measured at baseline and following the 10 week intervention period.
Secondary outcome [6] 393953 0
This is a primary outcome measure. Post-exertion malaise: a brief questionnaire which assess the frequency and severity of post-exertion malaise.. Participants rate each of 5 symptoms for frequency and then severity thus answering 10 questions in total.
Timepoint [6] 393953 0
Post-exertion malaise will be measured at baseline and following the 10 week intervention period.

Eligibility
Key inclusion criteria
Young people aged 13-18 years with a diagnosis of chronic fatigue syndrome made by a doctor.
The availability of a parent/caregiver is not a key inclusion criteria. Having a parent/caregiver available to answer questionnaires is preferred but not a requirement for a young person to participate in the study.
Minimum age
13 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Taking probiotics regularly
2. On immunosuppressant therapy
3. Participation in another intervention trial for CFS

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a placebo controlled trial.
Neither the participants nor the researchers will know which group (intervention or placebo) participants have been assigned to.

The randomisation schedule will be arranged and held by Fonterra Cooperative New Zealand who are supplying the capsules for this study. Fonterra will provide capsules in numbered bottles and hold the randomisation schedule at their site (different from the the research site) throughout the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created
by computer software
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
Parallel
Other design features
Due to the age of the study participants (13-18 years old), we will obtain consent from the parents/caregivers of young people aged 13-16 years old. For all young participants (13-18 years old) we are also planning to ask the parents or caregivers to answer questions regarding their own feelings, as well as their perception of their children/young person. Although the parents/caregivers will not be allocated a treatment (capsule), they will be asked to complete the Perceived Stress Scale to rate their own levels of stress, as well as the parent report versions of the Mood and Feelings questionnaire, the Pediatric Quality of Life Multidimensional Fatigue Scale, and the Post-exertion Malaise questionnaires.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
An intention to treat analysis will be conducted in SAS 9.4 using two sample t-tests to compare scores on the primary outcome measures between the probiotic and palcebo groups.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
19/04/2021
Actual
Date of last participant enrolment
Anticipated
31/07/2021
Actual
Date of last data collection
Anticipated
17/10/2021
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 23414 0
New Zealand
State/province [1] 23414 0
Auckland

Funding & Sponsors
Funding source category [1] 307678 0
Commercial sector/Industry
Name [1] 307678 0
Fonterra Co-operative Ltd.
Country [1] 307678 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Department of Psychological Medicine
University of Auckland
22-30 Park Avenue
Grafton
Auckland 1023
New Zealand
Country
New Zealand
Secondary sponsor category [1] 308377 0
None
Name [1] 308377 0
Address [1] 308377 0
Country [1] 308377 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307714 0
Health and Disability Ethics Committee
Ethics committee address [1] 307714 0
Health and Disability Ethics Committee
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 307714 0
New Zealand
Date submitted for ethics approval [1] 307714 0
28/01/2021
Approval date [1] 307714 0
25/03/2021
Ethics approval number [1] 307714 0
21/NTA/23

Summary
Brief summary
Chronic Fatigue Syndrome (CFS) is a debilitating disorder characterised by fatigue that does not improve with rest, physical symptoms of pain, nausea, fatigue, dizziness, headaches and post exertional malaise which is a worsening of CFS symptoms following minimal physical or mental effort. In young people, CFS can disrupt typical adolescent development by impacting a young person’s ability to attend school, socialise with peers, and maintain physical activity. Rates of depression and anxiety are also higher in those with CFS. Currently there is no treatment for CFS and patients are encouraged to manage symptoms. Gut microbiota are the colony of bacteria, fungi and viruses that live in the gastrointestinal tract and play a role in physiological processes in the body. The microbiota-gut-brain-axis refers to multiple bi-directional relationships between the microbes in the gut and the brain. Evidence suggests that disruption to the balance of beneficial versus pathological microbes in the gut (dysbiosis) is present in chronic fatigue, depression and anxiety. Probiotics, defined as live microorganisms that confer a benefit to the host when consumed, are one way in which the healthy balance of microbes can be restored in the gut. Preliminary studies have suggested that supplementation with probiotics can improve psychological well-being in people with CFS. To date there have not been any studies of the effect of probiotics in adolescents with CFS. This study aims to determine whether probiotic supplementation improves the psychological wellbeing of adolescents with CFS using a randomised, double blind placebo controlled intervention that comprises a 10-week supplementation period with a combination of the probiotics Lactobacillus rhamnosus HN001 and Bifidobacterium animalis HN019.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108242 0
Dr Rebecca Slykerman
Address 108242 0
Department of Psychological Medicine
Room 3033, Building 507
University of Auckland
22-30 Park Avenue
Grafton
Auckland 1023
New Zealand
Country 108242 0
New Zealand
Phone 108242 0
+64 9 923 1132
Fax 108242 0
Email 108242 0
[email protected]
Contact person for public queries
Name 108243 0
Dr Rebecca Slykerman
Address 108243 0
Department of Psychological Medicine
Room 3033, Building 507
University of Auckland
22-30 Park Avenue
Grafton
Auckland 1023
New Zealand
Country 108243 0
New Zealand
Phone 108243 0
+64 9 923 1132
Fax 108243 0
Email 108243 0
[email protected]
Contact person for scientific queries
Name 108244 0
Dr Rebecca Slykerman
Address 108244 0
Department of Psychological Medicine
Room 3033, Building 507
University of Auckland
22-30 Park Avenue
Grafton
Auckland 1023
New Zealand
Country 108244 0
New Zealand
Phone 108244 0
+64 9 923 1132
Fax 108244 0
Email 108244 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
In line with ethical guidelines only the research team will have access to individual level participant data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10371Study protocol  [email protected] 381296-(Uploaded-28-01-2021-10-03-27)-Study-related document.docx
10374Ethical approval  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.