In Vivo Investigation on Mitochondrial Dysfunction in Post-COVID Fatigue and Cancer Fatigue.

NCT05753228 | Unknown DMC

• 1 other identifier: DSRB 2022/00668
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

To date, little is understood regarding post-COVID fatigue or cancer fatigue though it is known to affect a large proportion of patients (10-70% depending on the population). This study aims to investigate potential mitochondrial function and metabolic changes in brain to provide further information regarding the etiology of these changes leading to fatigue. This study hypothesized that Post-COVID fatigue is ensued by perturbations in metabolism and mitochondrial function in the brain. This is a case-control study. In this study, 30 patients (experimental group) complaining of persistent fatigue lasting longer than 4 weeks after recovering from SARS-CoV-2 infection and the age/gender-matched control of 30 healthy subjects (control group 1) and 30 patients suffering from cancer-related fatigue patients longer than 4 weeks after remission (control group 2). Both the experimental group (post-COVID fatigue) and control group 2 (cancer fatigue) will be recruited from NUH outpatient clinic will undergo a session of MRI, 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS) and the Chalder Fatigue Scale, Health Questionnaire (EQ-5D-5L) and Hamilton Depression Rating Scale at baseline and follow-up visit.

Conditions

Mitochondrial Dysfunction; COVID-19; Fatigue

Keywords

Mitochondrial dysfunction; COVID-19 fatigue; Cancer fatigue

Outcome Measures

Primary Outcomes (4)

• MRI, 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS)

  The MRI, 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS) are used to assess metabolic and mitochondrial perturbations in post-COVID fatigue or cancer fatigue.

  90 minutes

• Chalder Fatigue Scale

  Chalder Fatigue Scale is a self-administered questionnaire for measuring the extent and severity of fatigue within both clinical and non-clinical, epidemiological populations. Each of the 11 items are answered on a 4-point scale ranging from the asymptomatic to maximum symptomology, such as 'Better than usual', 'No worse than usual', 'Worse than usual' and 'Much worse than usual'. For all items, the least symptomatic answers are on the left of the response-set, providing an easy-to-understand checklist for respondents. Using the Likert scoring method, responses on the extreme left receive a score of 0, increasing to 1, 2 or 3 as they become more symptomatic. The respondent's global score can range from 0 to 33. The global score also spans two dimensions-physical fatigue (measured by items 1-7) and psychological fatigue (measured by items 8-11). The Likert scoring system allows for means and distributions to be calculated for both the global total as well as the two sub-scales.

  5 minutes

• Health Questionnaire (EQ-5D-5L)

  The Health Questionnaire (EQ-5D-5L) is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from "no problems" through "extreme problems." The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.

  5 minutes

• Hamilton Depression Rating Scale

  The Hamilton Depression Rating Scale is used to quantify the severity of symptoms of depression and is one of the most widely used and accepted instruments for assessing depression. Method for scoring varies by version. For the HDRS17, a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher (indicating at least moderate severity) is usually required for entry into a clinical trial.

  10 minutes

Study Arms (3)

COVID fatigue patients

ACTIVE COMPARATOR

MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS),Chalder fatigue scale, Health Questionnaire (EQ-5D-5L), Hamilton Depression Rating Scale

Other: MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS); Other: Chalder Fatigue Scale; Other: Health Questionnaire (EQ-5D-5L); Other: Hamilton Depression Rating Scale

Cancer fatigue patients

ACTIVE COMPARATOR

MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS),Chalder fatigue scale, Health Questionnaire (EQ-5D-5L), Hamilton Depression Rating Scale

Other: MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS); Other: Chalder Fatigue Scale; Other: Health Questionnaire (EQ-5D-5L); Other: Hamilton Depression Rating Scale

Healthy patients as controls

ACTIVE COMPARATOR

MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS),Chalder fatigue scale, Health Questionnaire (EQ-5D-5L), Hamilton Depression Rating Scale

Other: MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS); Other: Chalder Fatigue Scale; Other: Health Questionnaire (EQ-5D-5L); Other: Hamilton Depression Rating Scale

Interventions

MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS) OTHER

MRI/ 3D Arterial Spin Labelling (ASL) and 1H magnetic resonance spectroscopy (MRS) to assess metabolic and mitochondrial perturbations in post-COVID fatigue or cancer fatigue.

COVID fatigue patients; Cancer fatigue patients; Healthy patients as controls

Chalder Fatigue Scale OTHER

The Chalder Fatigue Scale is used for measuring the extent and severity of fatigue within both clinical and non-clinical, epidemiological populations.

COVID fatigue patients; Cancer fatigue patients; Healthy patients as controls

Health Questionnaire (EQ-5D-5L) OTHER

The Health Questionnaire (EQ-5D-5L) is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from "no problems" through "extreme problems."

COVID fatigue patients; Cancer fatigue patients; Healthy patients as controls

Hamilton Depression Rating Scale OTHER

The Hamilton Depression Rating Scale is a multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery.

COVID fatigue patients; Cancer fatigue patients; Healthy patients as controls

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age between 21 and 70 years old (all 3 groups)
• SARS-COV-2 disease confirmed by PCR or ART (experimental group)
• Chalder Fatigue Score (CFQ-11): \>= 19 (experimental group and control group 2), =\< 11 (control group 1)
• able to understand the study purpose and consent to it (all 3 groups)

You may not qualify if:

• medically unstable
• contraindications for MR scanning (metallic implants, claustrophobia)
• requiring oxygen supplementation
• unable to follow instructions
• anemia (Hb \< 10g/dl)
• thyroid disorder
• neoplasm (applicable only to experimental group and control group 1)
• premorbid sleep disorder
• premorbid psychiatric disorders including depression
• pregnancy
• epilepsy

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National University of Singapore: collaborator

Study Sites (1)

Jeong Hoon K Lim

Singapore, 119074, Singapore

RECRUITING

Related Publications (8)

• Blomberg B, Mohn KG, Brokstad KA, Zhou F, Linchausen DW, Hansen BA, Lartey S, Onyango TB, Kuwelker K, Saevik M, Bartsch H, Tondel C, Kittang BR; Bergen COVID-19 Research Group; Cox RJ, Langeland N. Long COVID in a prospective cohort of home-isolated patients. Nat Med. 2021 Sep;27(9):1607-1613. doi: 10.1038/s41591-021-01433-3. Epub 2021 Jun 23.

  PMID: 34163090 BACKGROUND

• Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, Saligan LN. Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature. BBA Clin. 2014 Jun 1;1:12-23. doi: 10.1016/j.bbacli.2014.04.001.

  PMID: 25147756 BACKGROUND

• Logue JK, Franko NM, McCulloch DJ, McDonald D, Magedson A, Wolf CR, Chu HY. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021 Feb 1;4(2):e210830. doi: 10.1001/jamanetworkopen.2021.0830.

  PMID: 33606031 BACKGROUND

• Miller B, Silverstein A, Flores M, Cao K, Kumagai H, Mehta HH, Yen K, Kim SJ, Cohen P. Host mitochondrial transcriptome response to SARS-CoV-2 in multiple cell models and clinical samples. Sci Rep. 2021 Jan 8;11(1):3. doi: 10.1038/s41598-020-79552-z.

  PMID: 33420163 BACKGROUND

• Tomas C, Brown A, Strassheim V, Elson JL, Newton J, Manning P. Correction: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome. PLoS One. 2018 Feb 8;13(2):e0192817. doi: 10.1371/journal.pone.0192817. eCollection 2018.

  PMID: 29420633 BACKGROUND

• Tomas C, Lodge TA, Potter M, Elson JL, Newton JL, Morten KJ. Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test. Sci Rep. 2019 Aug 7;9(1):11464. doi: 10.1038/s41598-019-47966-z.

  PMID: 31391529 BACKGROUND

• Kantarci K, Reynolds G, Petersen RC, Boeve BF, Knopman DS, Edland SD, Smith GE, Ivnik RJ, Tangalos EG, Jack CR Jr. Proton MR spectroscopy in mild cognitive impairment and Alzheimer disease: comparison of 1.5 and 3 T. AJNR Am J Neuroradiol. 2003 May;24(5):843-9.

  PMID: 12748083 BACKGROUND

• Lin DD, Crawford TO, Barker PB. Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol. 2003 Jan;24(1):33-41.

  PMID: 12533324 BACKGROUND

MeSH Terms

Conditions

Mitochondrial Diseases; COVID-19; Fatigue

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Jeong Hoon K Lim, MD

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeong Hoon Lim, MD

CONTACT

+6585339725; jeong_hoon_lim@nuhs.edu.sg

Serene huang, MN

CONTACT

+6583998743; serene_huang@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Case-control study

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 3, 2023
• Study Start: December 9, 2022
• Primary Completion: December 8, 2023
• Study Completion: December 8, 2023
• Last Updated: March 3, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)