ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616000567426

Ethics application status

Approved

Date submitted

29/04/2016

Date registered

3/05/2016

Date last updated

10/01/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Mitochondrial agents in the treatment of chronic fatigue syndrome: a 20-week, open-label, intervention trial

Scientific title

Mitochondrial agents in the treatment of chronic fatigue syndrome: a 20-week, open-label, intervention trial

Secondary ID [1]

Nil Known

Universal Trial Number (UTN)

U1111-1182-4482

Trial acronym

INVIGOR8

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Chronic Fatigue Syndrome

Condition category

Condition code

Other

Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study aims to examine the efficacy of a novel, tolerable, and practical adjunctive intervention by examining a combination of agents acting on mitochondrial targets.

The trial will assess the efficacy and tolerability of twice daily dosing for 20-weeks of purpose-designed combination capsules taken orally providing a daily amount of: N-acetylcysteine (NAC) 2000 mg; Acetyl L-carnitine (ALC) 1000mg; ubiquinone (Co Q10) 200 mg; magnesium (as orotate 500mg) 64mg; calcium ascorbate dehydrate (equiv ascorbic acid 200mg) 242mg; cholecalciferol (equiv vitamin D3 250IU) 12.5micrograms; a-tocopherol (equiv natural vitamin E 50IU) 60IU; alpha lipoic acid 150mg; Retinyl palmitate (equiv vitamin A 3000IU) 900ugREIU; and vitamin B co-factors: biotin (vitamin H) (600micrograms), thiamin hydrochloride (100mg), riboflavin (100mg), nicotinamide (200mg), calcium pantothenate (100mg), pyridoxine hydrocholoride (100mg), folic acid (800micrograms), cyanocobalamin (vitamin B12) (800micrograms) in people diagnosed with CFS.

A capsule count will be done to determine compliance.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

No control group. Open Label.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Chalder Fatigue Scale (CFQ 11)

Timepoint [1]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [1]

Montgomery–Asberg Depression Rating Scale (MADRS).

Timepoint [1]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [2]

Short Form-12 Health Survey

Timepoint [2]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [3]

Insomnia Severity Scale (ISI)

Timepoint [3]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [4]

Work and Social Adjustment Scale (WSAS)

Timepoint [4]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [5]

International Physical Activity Questionnaire (IPAQ) – Short Form

Timepoint [5]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [6]

Clinical Global Scale – Severity

Timepoint [6]

Baseline, Week 4, Week 8, Week 12, Week 16 and Week 20

Secondary outcome [7]

Clinical Global Scale – Improvement

Timepoint [7]

Week 4, Week 8, Week 12, Week 16 and Week 20

Eligibility

Key inclusion criteria

a. Male and female patients aged 18 to 65 years,
b. Diagnosed with chronic fatigue syndrome by an independent physician (a letter or referral will be preferred to confirm diagnosis),
c. Fulfil criteria for CFS as per the US Centres for Disease Control and Prevention (CDC), which requires persistent, unexplained fatigue for at least 6 months, concurrent with at least four of the following, 1) Impaired memory/concentration, 2) Sore throat, new headaches, 3) Unfreshreshing sleep, muscle pain, 4) Multi-joint pain 5)Tender lymph nodes
6) Post-exertional malaise
d. Have capacity to consent to the study and comply with study procedures,
e. Be using effective contraception if female, sexually active and of childbearing age,
f. Participants currently under any form of therapy will need to have been on that therapy for at least four (4) weeks prior to enrolment.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

a. Patients with known or suspected active and unstable systemic medical disorder,
b. Patients who have a major depressive episode in the two years preceding the diagnosis of CFS,
c. Acute suicidality as indicated by a score of 5 or 6 on Item 10 of the MADRS (or at the discretion of Principal Investigator)
d. Patients with current diagnosis of a psychotic disorder, bipolar disorder, substance abuse/dependence, eating disorder, significant personality disorder,
e. Recent gastrointestinal ulcers or renal stones,
f. Individuals who are pregnant or lactating,
g. Individuals with a diagnosis of epilepsy,
h. Those who are currently taking any of the study preparations (a 2-week washout period will be required if participants currently taking the study preparations would like to take part) or over 200micrograms of selenium/day,
i. Individuals currently enrolled in any other intervention study,
j. Individuals needing warfarin or phenytoin,
k. Individuals who are intolerant to or have had an anaphylactic reaction to any components of the preparation,
l. Inability to comply with either the requirements of informed consent or the treatment protocol.

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)

Open label study, Not randomised. Participants allocated to intervention sequentially.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

N/A

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

20-week open-label intervention study of a combination therapy for patients with chronic fatigue syndrome. Participants will receive 20 weeks of daily treatment, adjunctive to treatment as usual, with assessment visits at baseline, W4, W8, W12, W16, and W20.

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Data analysis, including descriptive statistics, t-tests, multiple regression, logistic regression, chi-square test, and ANOVA will be conducted using SPSS. Analysis of all outcome measures will be performed at each time point. Repeated measures linear mixed models analysis will be used to test the effect on rate of change on primary and secondary outcome measures over time. Tests of significance will use a level of a = 0.05.

No formal sample size calculation was performed as the study is a pilot, open-label and exploratory in nature. As with most pilot studies, the sample size will be a sample of convenience as the study is unfunded and limited by resourcing.

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Lack of funding/staff/facilities

Date of first participant enrolment

Anticipated

3/05/2016

Actual

3/05/2016

Date of last participant enrolment

Anticipated

31/07/2017

Actual

27/10/2016

Date of last data collection

Anticipated

31/01/2017

Actual

Sample size

Target

30

Accrual to date

Final

10

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Melbourne Clinic - Richmond

Recruitment postcode(s) [1]

3121 - Richmond

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

N/A

Address [1]

N/A

Country [1]

Primary sponsor type

University

Name

The University of Melbourne

Address

Grattan st
Parkville 3052 VIC

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Melbourne Clinic Ethics Committee

Ethics committee address [1]

2 Salisbury St
Richmond 3121 VIC

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/01/2016

Approval date [1]

17/02/2016

Ethics approval number [1]

270

Summary

Brief summary

Chronic fatigue syndrome (CFS) is a prolonged multisystem illness, characterised by very poor stamina, delayed post-exertional fatigue, which adversely affects one’s functioning across numerous physical and mental domains. Current treatments for CFS include pharmacological (e.g. fluoxetine, rintatolimod, galantamine), psychological (e.g. cognitive behaviour therapy (CBT), adaptive pacing therapy), and lifestyle interventions. For many who remain in treatment, they continue to experience significant social, occupational, and functional impairment. Thus new treatment approaches are urgently needed. 
While significant fatigue remains a common complaint across numerous disorders, it is posited that CFS is related to metabolic dysfunction, mitochondrial dysfunction and impaired biogenesis, in turn related to oxidative stress and systemic inflammation. Mitochondria are structures within cells primarily responsible for energy generation, and are particularly active in oxygen-rich and highly energy dependent tissues, such as the brain. Recent research suggests that patients suffering from CFS may improve with the supplementation of mitochondrial nutrients and antioxidants. This supplementation may be associated with the reduction to mitochondrial membranes, restoring mitochondrial energy production, protecting cellular structures and enzymes from oxidative damage, and decreasing fatigue. Given that CFS is largely a heterogeneous illness associated with a complex and multifactorial aetiology, combined with the present state of available treatments, it is plausible that the introduction of a combination of metabolic therapies may have positive effects on mitochondrial dysfunction and lead to symptom improvement for CFS sufferers.

Trial website

N/A

Trial related presentations / publications

N/A

Public notes

Contacts

Principal investigator

Name

Dr Ranjit Menon

Address

The Melbourne Clinic Professorial Unit & The University of Melbourne
2 Salisbury St
Richmond
VIC 3121

Country

Australia

Phone

+61394874748

Fax

Email

drmenon@gmail.com

Contact person for public queries

Name

Jenifer Murphy

Address

The Melbourne Clinic Professorial Unit & The University of Melbourne
2 Salisbury St
Richmond
VIC 3121

Country

Australia

Phone

+61394874748

Fax

Email

jenifer.murphy@unimelb.edu.au

Contact person for scientific queries

Name

Jenifer Murphy

Address

The Melbourne Clinic Professorial Unit & The University of Melbourne
2 Salisbury St
Richmond
VIC 3121

Country

Australia

Phone

+61394874748

Fax

Email

jenifer.murphy@unimelb.edu.au

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.