NCT02293616

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jun 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 13, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 18, 2014

Completed
7 months until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
Last Updated

July 18, 2018

Status Verified

July 1, 2018

Enrollment Period

1.8 years

First QC Date

November 13, 2014

Last Update Submit

July 16, 2018

Conditions

Respiratory Failure

Keywords

ICURespiratory FailureWeaknessNitrate supplementation

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Plasma Nitrate and Nitrite Levels

    5 days

  • Skeletal muscle strength

    2 months

  • Hospital Length of Stay

    2 weeks

Study Arms (2)

Nitrate Rich

EXPERIMENTAL

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.

Dietary Supplement: Nitrate Rich Beetroot Juice

Nitrate Depleted

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo

Interventions

Nitrate Rich Beetroot JuiceDIETARY_SUPPLEMENT

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

Also known as: Beet It Shot®
Nitrate Rich
PlaceboDIETARY_SUPPLEMENT
Nitrate Depleted

Eligibility Criteria

Age56 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (16)

  • 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.

    PMID: 23873130BACKGROUND

  • 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.

    PMID: 3558716BACKGROUND

  • 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.

    PMID: 12472328BACKGROUND

  • 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.

    PMID: 12682465BACKGROUND

  • 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.

    PMID: 15596690BACKGROUND

  • 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.

    PMID: 15878473BACKGROUND

  • 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.

    PMID: 8126356BACKGROUND

  • 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.

    PMID: 12594312BACKGROUND

  • 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.

    PMID: 23174856BACKGROUND

  • 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.

    PMID: 21454745BACKGROUND

  • 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.

    PMID: 10029398BACKGROUND

  • 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.

    PMID: 17713409BACKGROUND

  • 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.

    PMID: 18167491BACKGROUND

  • 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.

    PMID: 14579546BACKGROUND

  • 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.

    PMID: 16932234BACKGROUND

  • 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.

    PMID: 34097055DERIVED

MeSH Terms

Conditions

Respiratory InsufficiencyAsthenia

Condition Hierarchy (Ancestors)

Respiration DisordersRespiratory Tract DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • D. Clark Files, MD

    Wake Forest University Health Sciences

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 13, 2014

First Posted

November 18, 2014

Study Start

June 1, 2015

Primary Completion

April 1, 2017

Study Completion

April 1, 2017

Last Updated

July 18, 2018

Record last verified: 2018-07

Data Sharing

IPD Sharing
Will not share

Locations

US(1)