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

Critical Illness Clinical Trial

— HMB-ICU  

Official title:

A Study to Investigate the Effect of Eta-hydroxy-beta-methylbutyrate (HMB) on Skeletal Muscle Wasting in Early Critical Illness

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03464708
• Other study ID #: 17/LO/1635
• Secondary ID: 2016-003557-15
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 18, 2018
• Est. completion date: August 2021

Study information

• Verified date: March 2021
• Source: Guy's and St Thomas' NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 68
• Est. completion date: August 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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) Any reason excluding ultrasound measurement being performed (x) Insufficient understanding of the trial by the legal representative (xi) Intolerance to lactose and/or milk protein allergy

Related Conditions & MeSH terms

• Cachexia
• Critical Illness
• Muscular Atrophy

Intervention

Dietary Supplement:
• HMB
Powder form

Other:
• Lactose (placebo)
Powder form

Locations

Country	Name	City	State
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Guy's and St Thomas' NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in rectus femoris cross-sectional area	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.	Study Day 10
Secondary	Change in rectus femoris cross-sectional area	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.	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
Secondary	Difference in muscle quality	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.	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
Secondary	Muscle strength	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	Study day 7, study day 10, ICU discharge (expected to be less than 10 days) and hospital discharge or 28 days (whichever comes first)
Secondary	Muscle strength	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	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
Secondary	Physical function	Physical function will be measured using the Chelsea Physical Assessment Score (CPAx) at study day 7, study day 10, ICU discharge and hospital discharge.	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
Secondary	Physical function	Physical function will be measured using the six-minute walk test at hospital discharge and 3-months post-hospital discharge.	Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge
Secondary	Physical function	Physical function will be measured using the short physical performance battery (SPPB) at hospital discharge and 3-months post-hospital discharge.	Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge
Secondary	Quality of life	Quality of life will be determined using the SF-36 survey at 3-months post-hospital discharge.	3-months post-hospital discharge
Secondary	Inflammation, cell damage and metabolic profile	Markers of inflammation, cell damage, and plasma metabolomics will be determined from plasma samples taken at study days 1, 7 and 10.	Study day 1, study day 7, study day 10