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A Study to Investigate the Effect of HMB on Skeletal Muscle Wasting in Early Critical Illness (HMB-ICU)

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ClinicalTrials.gov Identifier: NCT03464708
Recruitment Status : Recruiting
First Posted : March 14, 2018
Last Update Posted : July 26, 2018
Sponsor:
Information provided by (Responsible Party):
Guy's and St Thomas' NHS Foundation Trust

Brief Summary:
This study aims to investigate the effect of beta-hydroxy-beta-methylbutyrate (HMB) on skeletal muscle wasting, physical function, strength and quality of life in survivors of critical illness. In addition, protein turnover, muscle biology and muscle histology will be investigated.

Condition or disease Intervention/treatment Phase
Critical Illness Dietary Supplement: HMB Other: Lactose (placebo) Phase 2

Detailed Description:

This is a double blind, placebo controlled, randomised controlled trial with the primary objective of investigating the effect of HMB on skeletal muscle wasting in early critical illness. Secondary objectives include determining the effect of HMB on skeletal muscle quality, strength, function and quality of life in survivors of critical illness. In addition, the effect of HMB on muscle protein turnover, muscle protein signalling, muscle fibre size and protein:DNA ratio will be investigated in a sub-group of participants.

Eligible participants will be randomised to receive either 3 g/day HMB or 3 g/day placebo within 24 hours of admission to the Intensive Care Unit (ICU). This will be continued until hospital discharge or 28-days, whichever comes first.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double blind, placebo controlled, randomised controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind.
Primary Purpose: Prevention
Official Title: A Study to Investigate the Effect of Eta-hydroxy-beta-methylbutyrate (HMB) on Skeletal Muscle Wasting in Early Critical Illness
Actual Study Start Date : June 18, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
Experimental: HMB
HMB 3 g/day until hospital discharge or 28-days (whichever comes first). HMB to be provided in powder form and administered via enteral feeding tube whilst in the ICU and orally once able to eat and drink.
Dietary Supplement: HMB
Powder form
Other Name: beta-hydroxy-beta-methylbutyrate

Placebo Comparator: Placebo
Placebo (lactose) 3 g/day until hospital discharge or 28-days (whichever comes first). Placebo to be provided in powder form and administered via enteral feeding tube whilst in the ICU and orally once able to eat and drink.
Other: Lactose (placebo)
Powder form




Primary Outcome Measures :
  1. Change in rectus femoris cross-sectional area [ Time Frame: Study Day 10 ]
    Rectus femoris cross-sectional area will be measured using muscle ultrasound within 24 hours of admission to ICU and then again at study day 10. The difference between these measurements will then be determined.


Secondary Outcome Measures :
  1. Change in rectus femoris cross-sectional area [ Time Frame: Study day 7, ICU discharge (expected to be less than 10 days), hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Rectus femoris cross-sectional area will be measured using muscle ultrasound within 24 hours of admission to ICU and then again at study day 7, ICU discharge, hospital discharge and 3-months post-hospital discharge. The difference between these measurements will then be determined.

  2. Change in vastus lateralis cross-sectional area [ Time Frame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days), hospital discharge, 3-months post-hospital discharge ]
    Vastus lateralis cross-sectional area will be measured using muscle ultrasound within 24 hours of admission to ICU and then again at study day 7, study day 10, ICU discharge, hospital discharge and 3-months post-hospital discharge. The difference between these measurements will then be determined.

  3. Change in vastus lateralis depth [ Time Frame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days), hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Vastus lateralis depth will be measured using muscle ultrasound within 24 hours of admission to ICU and then again at study day 7, study day 10, ICU discharge, hospital discharge and 3-months post-hospital discharge. The difference between these measurements will then be determined.

  4. Difference in muscle quality [ Time Frame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days), hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Muscle quality will be measured determined by the echogenicity of the muscle, as measured using muscle ultrasound within 24 hours of admission to ICU and then again at study day 7,study day 10, ICU discharge, hospital discharge and 3-months post-hospital discharge. The difference between these measurements will then be determined.

  5. Muscle strength [ Time Frame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days) and hospital discharge or 28 days (whichever comes first) ]
    Muscle strength will be measured using the Medical Research Council (MRC) Sum Score at study day 7, study day 10, ICU discharge and hospital discharge

  6. Muscle strength [ Time Frame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days), hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Muscle strength will be measured using handgrip dynamometry at study day 7, study day 10, ICU discharge, hospital discharge and 3-months post-hospital discharge

  7. Physical function [ Time Frame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days), hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Physical function will be measured using the Chelsea Physical Assessment Score (CPAx) at study day 7, study day 10, ICU discharge and hospital discharge.

  8. Physical function [ Time Frame: Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Physical function will be measured using the six-minute walk test at hospital discharge and 3-months post-hospital discharge.

  9. Physical function [ Time Frame: Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge ]
    Physical function will be measured using the short physical performance battery (SPPB) at hospital discharge and 3-months post-hospital discharge.

  10. Quality of life [ Time Frame: 3-months post-hospital discharge ]
    Quality of life will be determined using the SF-36 survey at 3-months post-hospital discharge.

  11. Inflammation, cell damage and metabolic profile [ Time Frame: Study day 1, study day 7, study day 10 ]
    Markers of inflammation, cell damage, and metabolic profile will be determined from plasma samples taken at study days 1, 7 and 10.

  12. Muscle protein breakdown, muscle protein synthesis and protein signalling [ Time Frame: 7 days ]
    Muscle protein breakdown, muscle protein synthesis and protein signalling will be measured in a sub-group of 10 participants from each group over the first 7 days of ICU admission. This will be done using amino acid tracers and muscle biopsies.

  13. Muscle fibre cross-sectional area [ Time Frame: 7 days ]
    Muscle fibre cross-sectional area will be measured in a sub-group of 10 participants from each group over the first 7 days of ICU admission. This will be done using muscle biopsies.

  14. Muscle fibre type [ Time Frame: 7 days ]
    Muscle fibre type, will be measured in a sub-group of 10 participants from each group over the first 7 days of ICU admission. This will be done using muscle biopsies.

  15. Protein:DNA ratio [ Time Frame: 7 days ]
    Protein:DNA ratio will be measured in a sub-group of 10 participants from each group over the first 7 days of ICU admission. This will be done using muscle biopsies.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

(i) ≥18 years old (ii) Due to receive enteral nutrition via a nasogastric or naso-jejunal tube as part of routine care (iii) Receiving mechanical ventilation and likely to continue this for more than 48 hours (iv) Likely to remain on the ICU for >7 days (v) Likely to survive intensive care admission. (vi) Admitted to recruiting ICU <24 hours from hospital admission and referring ICU ≥7 days from hospital admission (vii) Agreement obtained from legal representative (viii) Able to comply with protocol and study procedures (ix) No known allergy to IMP or any of its excipients

Participants in other trials can be recruited where protocols are not deemed likely to interfere with endpoints of either study and agreement has been obtained from the respective Chief Investigators.

Since participants in the trial will be abstaining by virtue of their illness, contraception is not required as an eligibility requirement.

Exclusion Criteria:

(i) Pregnancy or breast feeding (ii) Active disseminated malignancy (diagnosed) (iii) Bilateral lower limb amputees (iv) Non-ambulant or acute unilateral lower limb amputees (v) Patients with a primary neuromyopathy (vi) Patients entered into trials of interventions which would affect muscle mass (vii) Patients assessed as requiring sole parenteral nutrition (viii) Admission to ICU within the previous 3 months (ix) Insufficient understanding of the trial by the legal representative (x) Intolerance to lactose and/or milk protein allergy

Additionally, patients who have significant coagulopathy (platelets < 40 000 or INR >1.6) as indicated on routine bloods at screening will not be eligible for muscle biopsy, but will be eligible for the amino acid tracer studies.

Patients with Phenylketonuria and known allergies to 13C6 labelled phenylalanine will not be eligible for the amino acid tracer studies.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03464708


Contacts
Contact: Danielle Bear, MRes 020 7188 5642 danielle.bear@gstt.nhs.uk
Contact: Elizabeth Bruna 020 7188 7188 ext 51682 Elizabeth.Bruna@gstt.nhs.uk

Locations
United Kingdom
Guy's and St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom, SE1 7EH
Contact: Elizabeth Bruna    0207 188 7188 ext 51682    Elizabeth.Bruna@gstt.nhs.uk   
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
Investigators
Principal Investigator: Nicholas Hart Guy's and St Thomas' NHS Foundation Trust

Responsible Party: Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03464708     History of Changes
Other Study ID Numbers: 17/LO/1635
2016-003557-15 ( EudraCT Number )
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: July 26, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Guy's and St Thomas' NHS Foundation Trust:
Critical illness
HMB
Nutrition
Muscle wasting
Recovery

Additional relevant MeSH terms:
Critical Illness
Cachexia
Wasting Syndrome
Muscular Atrophy
Disease Attributes
Pathologic Processes
Emaciation
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Metabolic Diseases
Nutrition Disorders
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical