Back to resultsA Study to Investigate the Effect of HMB on Skeletal Muscle Wasting in Early Critical Illness (HMB-ICU)
Primary Purpose
Critical Illness
Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
HMB
Lactose (placebo)
Sponsored by
About this trial
This is an interventional prevention trial for Critical Illness focused on measuring Critical illness, HMB, Nutrition, Muscle wasting, Recovery
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
Sites / Locations
- Guy's and St Thomas' NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HMB
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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
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
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.
Physical function
Physical function will be measured using the six-minute walk test at hospital discharge and 3-months post-hospital discharge.
Physical function
Physical function will be measured using the short physical performance battery (SPPB) at hospital discharge and 3-months post-hospital discharge.
Quality of life
Quality of life will be determined using the SF-36 survey at 3-months post-hospital discharge.
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.
Full Information
NCT ID
NCT03464708
First Posted
February 22, 2018
Last Updated
March 15, 2021
Sponsor
Guy's and St Thomas' NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT03464708
Brief Title
A Study to Investigate the Effect of HMB on Skeletal Muscle Wasting in Early Critical Illness
Acronym
HMB-ICU
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
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 18, 2018 (Actual)
Primary Completion Date
May 2021 (Anticipated)
Study Completion Date
August 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guy's and St Thomas' NHS Foundation Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness
Keywords
Critical illness, HMB, Nutrition, Muscle wasting, Recovery
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double blind, placebo controlled, randomised controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind.
Allocation
Randomized
Enrollment
68 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HMB
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
HMB
Other Intervention Name(s)
beta-hydroxy-beta-methylbutyrate
Intervention Description
Powder form
Intervention Type
Other
Intervention Name(s)
Lactose (placebo)
Intervention Description
Powder form
Primary Outcome Measure Information:
Title
Change in rectus femoris cross-sectional area
Description
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.
Time Frame
Study Day 10
Secondary Outcome Measure Information:
Title
Change in rectus femoris cross-sectional area
Description
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.
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
Title
Difference in muscle quality
Description
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.
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
Title
Muscle strength
Description
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
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)
Title
Muscle strength
Description
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
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
Title
Physical function
Description
Physical function will be measured using the Chelsea Physical Assessment Score (CPAx) at study day 7, study day 10, ICU discharge and hospital discharge.
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
Title
Physical function
Description
Physical function will be measured using the six-minute walk test at hospital discharge and 3-months post-hospital discharge.
Time Frame
Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge
Title
Physical function
Description
Physical function will be measured using the short physical performance battery (SPPB) at hospital discharge and 3-months post-hospital discharge.
Time Frame
Hospital discharge or 28 days (whichever comes first), 3-months post-hospital discharge
Title
Quality of life
Description
Quality of life will be determined using the SF-36 survey at 3-months post-hospital discharge.
Time Frame
3-months post-hospital discharge
Title
Inflammation, cell damage and metabolic profile
Description
Markers of inflammation, cell damage, and plasma metabolomics will be determined from plasma samples taken at study days 1, 7 and 10.
Time Frame
Study day 1, study day 7, study day 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas Hart
Organizational Affiliation
Guy's and St Thomas' NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Investigate the Effect of HMB on Skeletal Muscle Wasting in Early Critical Illness
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