Strength Testing After Nitrate Delivery (STAND) in ICU Patients

NCT ID: NCT02293616

Last Updated: 2018-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2017-04-30

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

Conditions

Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Nitrate Rich

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.

Group Type: EXPERIMENTAL

Nitrate Rich Beetroot Juice

Intervention Type: DIETARY_SUPPLEMENT

Nitrate rich beetroot juice diet supplement will be consumed by subjects.

Nitrate Depleted

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Interventions

Nitrate Rich Beetroot Juice

Nitrate rich beetroot juice diet supplement will be consumed by subjects.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Beet It Shot®

Eligibility Criteria

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

• Minimum Eligible Age: 56 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

D. Clark Files, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23873130 (View on PubMed)

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. doi: 10.1016/0021-9681(87)90171-8.

Reference Type: BACKGROUND

PMID: 3558716 (View on PubMed)

De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphael JC, Outin H, Bastuji-Garin S; Groupe de Reflexion et d'Etude des Neuromyopathies en Reanimation. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002 Dec 11;288(22):2859-67. doi: 10.1001/jama.288.22.2859.

Reference Type: BACKGROUND

PMID: 12472328 (View on PubMed)

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. doi: 10.1097/01.CCM.0000053651.38421.D9.

Reference Type: BACKGROUND

PMID: 12682465 (View on PubMed)

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. doi: 10.1378/chest.126.6.1897.

Reference Type: BACKGROUND

PMID: 15596690 (View on PubMed)

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. doi: 10.1016/j.jclinepi.2004.10.018.

Reference Type: BACKGROUND

PMID: 15878473 (View on PubMed)

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. doi: 10.1093/geronj/49.2.m85.

Reference Type: BACKGROUND

PMID: 8126356 (View on PubMed)

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. doi: 10.1056/NEJMoa022450.

Reference Type: BACKGROUND

PMID: 12594312 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23174856 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21454745 (View on PubMed)

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. doi: 10.1097/00006199-199901000-00004.

Reference Type: BACKGROUND

PMID: 10029398 (View on PubMed)

Luiking YC, Deutz NE. Exogenous arginine in sepsis. Crit Care Med. 2007 Sep;35(9 Suppl):S557-63. doi: 10.1097/01.CCM.0000279191.44730.A2.

Reference Type: BACKGROUND

PMID: 17713409 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18167491 (View on PubMed)

Mensinga TT, Speijers GJ, Meulenbelt J. Health implications of exposure to environmental nitrogenous compounds. Toxicol Rev. 2003;22(1):41-51. doi: 10.2165/00139709-200322010-00005.

Reference Type: BACKGROUND

PMID: 14579546 (View on PubMed)

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. doi: 10.1097/01.CCM.0000240233.01711.D9.

Reference Type: BACKGROUND

PMID: 16932234 (View on PubMed)

Gandotra S, Files DC, Shields KL, Berry M, Bakhru RN. Activity Levels in Survivors of the Intensive Care Unit. Phys Ther. 2021 Sep 1;101(9):pzab135. doi: 10.1093/ptj/pzab135.

Reference Type: DERIVED

PMID: 34097055 (View on PubMed)

Other Identifiers

IRB00030880

Identifier Type: -

Identifier Source: org_study_id