Optimal Protein Supplementation and Early Exercise In Mechanically Ventilated Patients

Sponsor

National University Hospital, Singapore (Other)

Overall Status

Recruiting

CT.gov ID

NCT05603585

Collaborator

National University, Singapore (Other)

150

Enrollment

Location

Arms

6.8

Anticipated Duration (Months)

22.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Pilot Randomized Controlled Trial (RCT) will be conducted where where mechanically ventilated patients will be randomized to optimal protein (Achieve 80% protein supplementation adequacy with daily titration) versus standard protein feeding. Both groups will receive standard usual early exercise therapy.

Specific aim 1: To determine if optimal protein supplementation improves functional outcome of patients as measured by Functional Status Score (FSS) on Day 7.

Specific aim 2: To determine if optimal protein supplementation reduces muscle loss of patients at Day 7 as measured by the Rectus Femoris thickness and cross-sectional area (RFCSA) using skeletal muscle ultrasound.

Specific aim 3: To determine difference in functional recovery between groups using quality of life (QOL) scores and 6-minute walk distance at 3 months after hospital discharge.

The hypothesis is protein inadequacy can be overcome with optimized protein supplementation to reduce muscle loss/sarcopenia and functional impairment in ICU survivors.

Condition or Disease	Intervention/Treatment	Phase
Nutritional Deficiency Cachexia	Dietary Supplement: Optimal protein supplementation to achieve 80% protein adequacy.	N/A

Detailed Description

This study will be a prospective pilot randomized controlled trial. Collaboration will be between the National University Hospital (Medical, Surgical and Cardiothoracic ICUs), Centre for Healthy Aging, National University Health System (NUHS) and Physical Education & Sports Science, National Institute of Education (NIE). Patients admitted into these ICUs will be screened and those meeting the inclusion criteria will be approached for consent. If the patient is unable to consent, his/her legally acceptable representatives will be approached. This approach is routinely done in ICU studies. As with other ICU studies, potential difficulties in consenting and recruiting patients will be expected. To overcome this, all adult ICU patients at NUH will be included in the current study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Eligible patients will be randomly assigned to receive either standard feeding or optimised protein feeding based on random permuted blocks with age (≥65 years or < 65 years) and ICU site of recruitment as the stratification factors. The primary endpoint is difference in FSS between the two groups at Day 7.Eligible patients will be randomly assigned to receive either standard feeding or optimised protein feeding based on random permuted blocks with age (≥65 years or < 65 years) and ICU site of recruitment as the stratification factors. The primary endpoint is difference in FSS between the two groups at Day 7.

Masking:

Single (Participant)

Masking Description:

The participants and their legally acceptable representative will not be made known of the experimental arms that the participant is allocated to.

Primary Purpose:

Prevention

Official Title:

Attenuation of Sarcopenia Using Optimal Protein Supplementation and Early Exercise In Mechanically Ventilated Patients: A Pilot Randomized Controlled Trial (PIVOT)

Actual Study Start Date :

Sep 6, 2022

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Group Standard care as per current ICU feeding regime.
Experimental: Interventional Group Optimal protein supplementation to achieve 80% protein adequacy through optimised protein supplementation. The protein supplementation will be increased/decreased based on the previous day's intake to achieve 80% adequacy each day by the dietician.	Dietary Supplement: Optimal protein supplementation to achieve 80% protein adequacy. Additional protein required and delivered by adding protein powder and given in bolus feeds

Arm

Intervention/Treatment

No Intervention: Control Group

Standard care as per current ICU feeding regime.

Experimental: Interventional Group

Optimal protein supplementation to achieve 80% protein adequacy through optimised protein supplementation. The protein supplementation will be increased/decreased based on the previous day's intake to achieve 80% adequacy each day by the dietician.

Dietary Supplement: Optimal protein supplementation to achieve 80% protein adequacy.

Additional protein required and delivered by adding protein powder and given in bolus feeds

Outcome Measures

Primary Outcome Measures

Functional Status Score for ICU (FSS-ICU) [Day 1 of Randomisation; Day 7 of Randomisation; Day of ICU Discharge , approximately 14 days after ICU admission]
It is an ordinal score consisting of 5 activities (namely, Rolling in bed, Supine to Sit Transfer, Sit to Stand Transfer, Sitting Edge of Bed, Walking); each activity is scored from 0 to 7 to a total of 35. A higher score indicates a better functioning. It closely resembles Activities of Daily Living (ADL) and it is possible to even measure the pre-admission score. The FSS-ICU is measured at day 1 upon recruitment and compared to a one week period and to the time of discharge in intensive care to determine functional improvements at these time points.

Secondary Outcome Measures

Rectus Femoris Cross-Sectional Area (RFCSA) and anterior thigh and rectus femoris thickness [Day 1 of Randomisation; Day 4 of Randomisation; Day 7 of Randomisation; Day of ICU Discharge , approximately 14 days after ICU admission]
RFCSA correlates well with quadriceps strength, measured by B-mode ultrasonography using linear transducer array. Pennation angle will also be calculated. The rectus femoris RFCSA and thigh thickness and pennation angle is measured at day 1 upon recruitment and compared to day 4 and then day 7 of study recruitment to determine changes in muscle loss.
Six-Minute Walk Test (6MWT) [3 months post hospital discharge]
Feasible standard measure of exercise capacity
Clinical Frailty Index (CFI) [Day 1 of Randomisation; Day of ICU Discharge , approximately 14 days after ICU admission]
The CFI scoring is a scale from 1 to 9, 1 being very fit (best outcome) while 9 being terminally ill (worst outcome). The CFI is measured at day 1 upon recruitment and compared to point of ICU discharge to determine changes in frailty.
Blood Biomarkers [Day 1 of Randomisation; Day 4 of Randomisation]
The following cytokines; IL-6, IL-10, IL-12 and TNF-1α and MCP1, HMGB1 will be analysed via blood test to monitor inflammatory reactions
Indirect calorimetry (IC) [Day 1 to Day 7 of Randomisation (daily or till extubation)]
Gold standard for measurement of energy expenditure (EE)

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 21 years and above.
Expected mechanical ventilation duration ≥ 72hours (to allow for inclusion of those with ICU stay of at least 3 days as increased MV dependence might increase global weakness).
Expected to stay in hospital for ≥ 7days (to allow for inclusion of those with bedrest of more than 7 days as would increase the likelihood of muscle loss).

Exclusion Criteria:

Pregnant woman.
Amputation of either lower limbs.
Surgery of lower limb during the current admission.
Any neurological/rheumatologic/orthopaedic/burn problem that may impact or confound rehabilitation.
Patient not able to feed by 48 hours AND not given parenteral feeding.
Patients on Continuous Renal Replacement Therapy.
Sepsis with poor prognosis.
Moribund within 48hours.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National University Hospital	Singapore		Singapore	119074

Sponsors and Collaborators

National University Hospital, Singapore
National University, Singapore

Investigators

Principal Investigator: Geetha Kayambu, National University Hospital, Singapore

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National University Hospital, Singapore

ClinicalTrials.gov Identifier:

NCT05603585

Other Study ID Numbers:

2021/00201

First Posted:

Nov 2, 2022

Last Update Posted:

Nov 2, 2022

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Malnutrition

Cachexia

Study Results

No Results Posted as of Nov 2, 2022