Strength Testing After Nitrate Delivery (STAND) in ICU Patients

Not Applicable

Completed

Interventions: Dietary Supplement: Placebo
Dietary Supplement: Nitrate Rich Beetroot Juice

Brief Summary: It is well documented that intensive care unit (ICU) patients have lower levels of skeletal muscle strength compared to non-ICU patients upon hospital discharge, and this weakness affects the patient's ability to perform basic activities of daily living upon hospital discharge and for extended periods thereafter. Recently, critically ill ICU patients have been shown to have lower nitric oxide levels. These patients often suffer from a disturbed homeostasis with circulatory and metabolic abnormalities that may potentially contribute to their ICU acquired weakness. Given the recent research showing dietary nitrate supplementation can increase nitric oxide levels and improve exercise tolerance in healthy and diseased older individuals, our aim is to investigate the importance of nitrate supplementation in ICU patients with focus on physical function and ICU acquired muscle weakness.

Detailed Description: The proposed study is an investigator initiated, double blind, placebo controlled experimental study designed to evaluate the effect of chronic NO3- supplementation via beetroot juice ingestion on the skeletal muscle strength and physical function in ICU patients. Patients will be randomized to receive either nitrate rich or nitrate depleted beetroot juice once daily during their ICU and hospital stay. Physical function and skeletal muscle strength will be measured at ICU (± 2 days) and hospital (± 2 days) discharge and 2 months (± 2 weeks) after enrollment. Plasma levels of nitrate and nitrite will be measured 1, 3 and 5 days after randomization into the trial and at ICU and hospital discharge. Skeletal muscle ultrasound will be performed to examine the size and echogenicity of patient muscles. Self-reported physical function will be measured using the Functional Performance Inventory Short Form (FPI-SF). The FPI-SF provides an overall score of patient self-reported functional performance in the areas of household maintenance, movement, family and social activities, work, avocation and recreation

Recruitment & Eligibility

Inclusion Criteria

Age > 55 years
Mechanically ventilated via an endotracheal tube or mask who have begun spontaneous breathing trials or extubated within the previous 24 hours
Lung Injury as defined by a PaO2 / FiO2 < 300

Exclusion Criteria

Inability to walk without assistance prior to acute ICU illness (use of a cane or walkers not exclusions)
Cognitive impairment prior to acute ICU illness (non-verbal)
Acute stroke
Body mass index (BMI) >50
Neuromuscular disease that could impair weaning (myasthenia gravis, ALS, Guillain-Barre)
Hip fracture, unstable cervical spine or pathological fracture
Mechanically Ventilated > 80 hours
Current hospitalization or transferring hospital stay > 7 days
DNR/DNI on admission
Cancer treatment within the last 6 months
Moribund
Participation in another research study
On nitroglycerine or nitrate preparations used with angina or phosphodiesterase type 5 inhibitors
Body mass less than 60 kg

Arm && Interventions

Group	Intervention	Description
Nitrate Depleted	Placebo	This group will consume a beetroot juice supplement (Beet It Shot®, James White Drinks, UK) that has had the nitrate removed from the beverage by the manufacturer. Patient's diet will be supplemented once daily with one 70 ml bottle while hospitalized up to 14 days.
Nitrate Rich	Nitrate Rich Beetroot Juice	A nitrate rich beetroot juice supplement (Beet It Shot®, James White Drinks, UK) high in nitrates will be provided to the subjects. Subject's diet will be supplemented once daily while hospitalized up to 14 days with one 70 ml bottle containing 300 mg of dietary nitrate.

Primary Outcome Measures

Name	Time	Method
physical function assessed using the Short Physical Performance Battery (SPPB)	2 months	The SPPB is based on timed measures of standing balance, walking speed, and ability to rise from a chair. Each performance measure is assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 inability to complete the test. A summary score (range 0-12) will be calculated by adding the three scores.

Secondary Outcome Measures

Name	Time	Method
Plasma Nitrate and Nitrite Levels	5 days	Blood samples will be collected in 4 mL lithium heparin vials. Nitrate and nitrite will be measured separately using the ENO-20 NOx analyzer.
Skeletal muscle strength	2 months	Skeletal muscle strength will be measured in both upper and lower extremities. Hand grip strength in both hands will be measured using a hand held grip strength dynamometer. Additionally, an electronic strength dynamometer will be used to collect strength measures of the elbow flexion, elbow extension, shoulder flexion in the scaption plane, ankle dorsiflexion, knee extension and hip extension, bilaterally. Skeletal muscle ultrasound will be performed on upper and lower extremities bilaterally.
Hospital Length of Stay	2 weeks	The hospital calendar days (or any portion of a calendar day) at the enrolling hospital and at any long term acute care facility to which the subject is directly transferred.

Locations (1): Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States