Mitochondrial Assessment in Critical Ill Patients in Intensive Care

NCT07018843 | Not Yet Recruiting DMC

• 1 other identifier: RHM CRI0453
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Critically ill patients often require admission to the intensive care unit (ICU). When patients develop organ failures and end up on a ventilator, there are changes in the body's cell function that can increase the risk of poor outcomes. All cells, in order to function normally, have mitochondria, which help them generate energy and transfer vital messages between cells. However, during critical illness, the mitochondria in the cells can function less effectively and die prematurely, or their new synthesis and regeneration can be severely affected. This can result in continuous multi-organ failure with a lack of recovery and muscle wasting, causing severe weakness and an inability to function normally. In this study, the investigators aim to assess mitochondrial capacity using three methods with varying levels of invasiveness. The investigators are planning to recruit 20 patients in the ICU who are on a ventilator for breathing support. The investigators plan to measure mitochondrial capacity from a breath test, blood cells, and muscle cells. The investigators will collect breath samples after consuming an amino acid, which is a component of protein in our body and is commonly found in food. This amino acid is only broken down by the mitochondria. This safe test allows us to measure how much mitochondrial capacity remains in the body after the modified amino acid is broken down by the mitochondria. In comparison, the investigators will use standard methods which includes blood tests and muscle biopsy to examine the mitochondrial function of platelets (blood cells) and muscle cells. The investigators will also use non-invasive techniques (ultrasound and 'MyotonPRO') to assess muscle. This study will help us determine the best way to assess mitochondrial function and capacity in critically ill patients and to understand strengths and weaknesses of different approaches. When patients' mitochondrial function or capacity is impaired, the investigators can provide them with particular nutrition to improve mitochondrial activity. Because evaluating this at the bedside is challenging, it is impossible to tell which patients may benefit from specific therapies that improve mitochondrial function. If this breath test provides an assessment similar to the standard, sophisticated mitochondrial testing, the investigators could use it at the bedside in the future, which may improve patient outcomes and help design large clinical trials.

Conditions

Critical Illness

Keywords

Mitochondria; Critical illness; Respirometry; Muscle biopsy; Breath test; Oroboros; MyotonPRO; Muscle ultrasound

Outcome Measures

Primary Outcomes (1)

• Feasibility of assessing mitochondrial capacity by three different methods

  Feasibility of assessing mitochondrial capacity in critically ill patients from different biological samples \[skeletal muscle, platelets and breath\] by three different methods, assessing the proportion of successful participants recruited, samples taken, and samples processed. The physiologic parameter used to assess each of these methods is detailed further below.

  15 months

Secondary Outcomes (5)

• To evaluate mitochondrial capacity using 13C-ketoisocaproate breath test.

  15 months

• To evaluate mitochondrial capacity using mitochondrial respiration in skeletal muscle

  15 months

• To evaluate mitochondrial capacity using the mitochondrial respiration of platelets

  15 months

• Longitudinal assessment of mitochondrial capacity in critical illness

  15 months

• Comparison of mitochondrial capacity across the secondary outcome measures.

  15 months

Other Outcomes (8)

• Exploratory outcome 1: To assess targeted and untargeted metabolomics in critically ill patients using analysis of the metabolites in biological samples collected.

  15 months

• Exploratory outcome 2: To assess mitochondrial specific metabolic markers in critically ill patients

  15 months

• Exploratory outcome 3: To assess oxidative stress in critically ill patients

  15 months

Study Arms (1)

Critically unwell intubated adults on ICU

The participants must be over 18, recruited within 48-hours of intubation and likely to remain intubated and ventilated for \> 72-hours.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Critically ill adult (\>18 years) patients who have been mechanically ventilated will be recruited from the Intensive Care Unit at University Hospital Southampton.

You may qualify if:

• Adults ≥ 18 years
• Mechanically ventilated at time of recruitment
• Defined as critically ill by the responsible clinician
• Recruited within 48-hours of intubation
• Likely to remain intubated and ventilated for \> 72-hours

You may not qualify if:

• Patients \< 18 years
• Patient is being treated on an end-of-life pathway or active treatment is likely to be withdrawn within 24-hours
• Patient has significant liver dysfunction (Child-Pugh ≥ class 3)
• Patient is not absorbing enterally (defined as 2 x NG aspirates of \> 500ml)
• Known pregnancy or positive urinary pregnancy test on testing

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead

Study Sites (1)

University Hospital Southampton

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Related Publications (12)

• Afolabi PR, Scorletti E, Smith DE, Almehmadi AA, Calder PC, Byrne CD. The characterisation of hepatic mitochondrial function in patients with non-alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test. J Breath Res. 2018 Jul 19;12(4):046002. doi: 10.1088/1752-7163/aacf12.

  PMID: 29943733 BACKGROUND

• Deane CS, Willis CRG, Phillips BE, Atherton PJ, Harries LW, Ames RM, Szewczyk NJ, Etheridge T. Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans. J Cachexia Sarcopenia Muscle. 2021 Jun;12(3):629-645. doi: 10.1002/jcsm.12706. Epub 2021 May 5.

  PMID: 33951310 BACKGROUND

• Deane CS, Phillips BE, Willis CRG, Wilkinson DJ, Smith K, Higashitani N, Williams JP, Szewczyk NJ, Atherton PJ, Higashitani A, Etheridge T. Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age. Geroscience. 2023 Jun;45(3):1271-1287. doi: 10.1007/s11357-022-00658-5. Epub 2022 Sep 26.

  PMID: 36161583 BACKGROUND

• Deane CS, Ames RM, Phillips BE, Weedon MN, Willis CRG, Boereboom C, Abdulla H, Bukhari SSI, Lund JN, Williams JP, Wilkinson DJ, Smith K, Gallagher IJ, Kadi F, Szewczyk NJ, Atherton PJ, Etheridge T. The acute transcriptional response to resistance exercise: impact of age and contraction mode. Aging (Albany NY). 2019 Apr 15;11(7):2111-2126. doi: 10.18632/aging.101904.

  PMID: 30996129 BACKGROUND

• Puthucheary ZA, Astin R, Mcphail MJW, Saeed S, Pasha Y, Bear DE, Constantin D, Velloso C, Manning S, Calvert L, Singer M, Batterham RL, Gomez-Romero M, Holmes E, Steiner MC, Atherton PJ, Greenhaff P, Edwards LM, Smith K, Harridge SD, Hart N, Montgomery HE. Metabolic phenotype of skeletal muscle in early critical illness. Thorax. 2018 Oct;73(10):926-935. doi: 10.1136/thoraxjnl-2017-211073. Epub 2018 Jul 6.

  PMID: 29980655 BACKGROUND

• Lee ZY, Ong SP, Ng CC, Yap CSL, Engkasan JP, Barakatun-Nisak MY, Heyland DK, Hasan MS. Association between ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality in mechanically ventilated critically ill patient: A single-center prospective observational study. Clin Nutr. 2021 Mar;40(3):1338-1347. doi: 10.1016/j.clnu.2020.08.022. Epub 2020 Aug 28.

  PMID: 32919818 BACKGROUND

• Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. doi: 10.1001/jama.2013.278481.

  PMID: 24108501 BACKGROUND

• Jameson TSO, Caldow MK, Stephens F, Denehy L, Lynch GS, Koopman R, Krajcova A, Urban T, Berney S, Duska F, Puthucheary Z. Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients. Crit Care. 2023 Nov 6;27(1):428. doi: 10.1186/s13054-023-04664-7.

  PMID: 37932834 BACKGROUND

• Supinski GS, Schroder EA, Callahan LA. Mitochondria and Critical Illness. Chest. 2020 Feb;157(2):310-322. doi: 10.1016/j.chest.2019.08.2182. Epub 2019 Sep 5.

  PMID: 31494084 BACKGROUND

• Klawitter F, Ehler J, Bajorat R, Patejdl R. Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review. Int J Mol Sci. 2023 Mar 14;24(6):5516. doi: 10.3390/ijms24065516.

  PMID: 36982590 BACKGROUND

• Zambon M, Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 2008 May;133(5):1120-7. doi: 10.1378/chest.07-2134. Epub 2008 Feb 8.

  PMID: 18263687 BACKGROUND

• Morgan A. Long-term outcomes from critical care. Surgery (Oxf). 2021 Jan;39(1):53-57. doi: 10.1016/j.mpsur.2020.11.005. Epub 2020 Dec 17.

  PMID: 33519011 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

1. Platelet specimens 2. Muscle biopsy specimens

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ahilanandan Dushianthan, MBBS MRCP PhD

  University of Southampton; University Hospital Southampton

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahilanandan Dushianthan, MBBS MRCP PhD

CONTACT

+447903943418; a.dushianthan@soton.ac.uk

Olivia Cox, MBBS

CONTACT

+447837374958; olivia.cox@uhs.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2025
• First Posted: June 13, 2025
• Study Start: July 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: March 1, 2026
• Last Updated: June 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)