Clinical trial NCT03464708: A Study to Investigate the Effect of HMB on Skeletal Muscle Wasting in Early Critical Illness
Official title: A Study to Investigate the Effect of Eta-hydroxy-beta-methylbutyrate (HMB) on Skeletal Muscle Wasting in Early Critical Illness
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Critical Illness
Keywords: Critical illness
HMB
Nutrition
Muscle wasting
Recovery
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2018-03-14
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, placebo controlled, randomised controlled trial
Primary purpose: PREVENTION

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.

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.

Eligibility 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) 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

Primary outcomes:
measure: Change in rectus femoris cross-sectional area
timeFrame: Study Day 10
Secondary outcomes:
measure: Change in rectus femoris cross-sectional area
timeFrame: 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
measure: Difference in muscle quality
timeFrame: 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
measure: Muscle strength
timeFrame: Study day 7, study day 10, ICU discharge (expected to be less than 10 days) and hospital discharge or 28 days (whichever comes first)
measure: Muscle strength
timeFrame: 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
measure: Physical function
timeFrame: 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
measure: Physical function
timeFrame: Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge
measure: Physical function
timeFrame: Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge
measure: Quality of life
timeFrame: 3-months post-hospital discharge
measure: Inflammation, cell damage and metabolic profile
timeFrame: Study day 1, study day 7, study day 10
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Nicholas Hart
role: PRINCIPAL_INVESTIGATOR
References: