Strength Testing After Nitrate Delivery (STAND) in ICU Patients

Respiratory Failure Clinical Trial

Official title:

Strength Testing After Nitrate Delivery (STAND) in ICU Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02293616
• Other study ID #: IRB00030880
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: April 2017

Study information

• Verified date: July 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 56 Years and older

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

Related Conditions & MeSH terms

• Respiratory Failure
• Respiratory Insufficiency

Intervention

Dietary Supplement:
• Nitrate Rich Beetroot Juice
Nitrate rich beetroot juice diet supplement will be consumed by subjects.
• Placebo

Locations

Country	Name	City	State
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (15)

Berry MJ, Morris PE. Early exercise rehabilitation of muscle weakness in acute respiratory failure patients. Exerc Sport Sci Rev. 2013 Oct;41(4):208-15. doi: 10.1097/JES.0b013e3182a4e67c. Review. — View Citation

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. — View Citation

De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphaël JC, Outin H, Bastuji-Garin S; Groupe de Réflexion et d'Etude des Neuromyopathies en Réanimation. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002 Dec 11;288(22):2859-67. — View Citation

Fletcher SN, Kennedy DD, Ghosh IR, Misra VP, Kiff K, Coakley JH, Hinds CJ. Persistent neuromuscular and neurophysiologic abnormalities in long-term survivors of prolonged critical illness. Crit Care Med. 2003 Apr;31(4):1012-6. — View Citation

Garland A, Dawson NV, Altmann I, Thomas CL, Phillips RS, Tsevat J, Desbiens NA, Bellamy PE, Knaus WA, Connors AF Jr; SUPPORT Investigators. Outcomes up to 5 years after severe, acute respiratory failure. Chest. 2004 Dec;126(6):1897-904. — View Citation

Groll DL, To T, Bombardier C, Wright JG. The development of a comorbidity index with physical function as the outcome. J Clin Epidemiol. 2005 Jun;58(6):595-602. Review. — View Citation

Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994 Mar;49(2):M85-94. — View Citation

Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003 Feb 20;348(8):683-93. — View Citation

Kelly J, Fulford J, Vanhatalo A, Blackwell JR, French O, Bailey SJ, Gilchrist M, Winyard PG, Jones AM. Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults. Am J Physiol Regul Integr Comp Physiol. 2013 Jan 15;304(2):R73-83. doi: 10.1152/ajpregu.00406.2012. Epub 2012 Nov 21. — View Citation

Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol (1985). 2011 Jun;110(6):1582-91. doi: 10.1152/japplphysiol.00071.2011. Epub 2011 Mar 31. — View Citation

Leidy NK. Psychometric properties of the functional performance inventory in patients with chronic obstructive pulmonary disease. Nurs Res. 1999 Jan-Feb;48(1):20-8. — View Citation

Luiking YC, Deutz NE. Exogenous arginine in sepsis. Crit Care Med. 2007 Sep;35(9 Suppl):S557-63. Review. — View Citation

Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008 Feb;7(2):156-67. doi: 10.1038/nrd2466. Review. — View Citation

Mensinga TT, Speijers GJ, Meulenbelt J. Health implications of exposure to environmental nitrogenous compounds. Toxicol Rev. 2003;22(1):41-51. Review. — View Citation

Zimmerman JE, Kramer AA, McNair DS, Malila FM, Shaffer VL. Intensive care unit length of stay: Benchmarking based on Acute Physiology and Chronic Health Evaluation (APACHE) IV. Crit Care Med. 2006 Oct;34(10):2517-29. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	physical function assessed using the Short Physical Performance Battery (SPPB)	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.	2 months
Secondary	Plasma Nitrate and Nitrite Levels	Blood samples will be collected in 4 mL lithium heparin vials. Nitrate and nitrite will be measured separately using the ENO-20 NOx analyzer.	5 days
Secondary	Skeletal muscle strength	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.	2 months
Secondary	Hospital Length of Stay	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.	2 weeks