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Strategies to Reduce Organic Muscle Atrophy in the Intensive Care Unit (STROMA-ICU)

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ClinicalTrials.gov Identifier: NCT02773771
Recruitment Status : Withdrawn (Per IRB submission history, submission declined and withdrawn. PI no longer at institution.)
First Posted : May 16, 2016
Last Update Posted : May 5, 2021
Sponsor:
Information provided by (Responsible Party):
Massachusetts General Hospital

Brief Summary:

Acute muscle wasting occurs early and rapidly during the first week of critical illness and contributes substantially to weakness acquired in the ICU. Muscle wasting and subsequent weakness is associated with delayed liberation from mechanical ventilation, prolonged hospital length of stay, long-term functional disability, and worse quality of life. Moreover, low muscle volume as well as ICU-acquired weakness increases the risk of mortality in critically ill patients. Although several factors likely accelerate skeletal muscle wasting during critical illness (e.g., immobility, inflammation, multi-organ failure), the understanding of the underlying mechanisms remains limited and is reflected in the lack of effective interventions to prevent the loss of muscle mass in ICU patients. To-date, there is no known safe and effective pharmacological or nutritional intervention to attenuate the acute loss of muscle mass in ICU patients.

Leucine is an amino acid widely regarded for its anabolic effects on muscle metabolism. However, the concentrations required to maximize its anti-proteolytic effects are far greater than the concentrations required to maximally stimulate protein synthesis. This has resulted in the search for leucine metabolites that may also be potent mediators of anabolic processes in skeletal muscle; one such compound is β-hydroxy-β-methylbutyrate (HMB). HMB is thought to primarily facilitate protein synthesis through stimulation of mammalian target of rapamycin (mTOR), a protein kinase responsive to mechanical, hormonal, and nutritional stimuli that plays a central role in the control of cell growth. Randomized, controlled trials to assess the effect of HMB supplementation on clinical outcomes in patients with chronic diseases are limited, and even fewer studies have assessed its effects on skeletal muscle metabolism during critical illness. Furthermore, despite compelling preclinical evidence, the exact mechanisms underlying the effect of HMB supplementation during acute catabolic stress in humans is not well defined. Therefore, the investigators goal is to study the impact of early HMB supplementation on skeletal muscle mass in ICU patients and to explore the mechanisms by which HMB may exert its effects on skeletal muscle metabolism during critical illness.


Condition or disease Intervention/treatment Phase
Muscle Atrophy Dietary Supplement: beta-hydroxy-beta-methylbutyrate Dietary Supplement: Placebo Dietary Supplement: Vital HP® Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Strategies to Reduce Organic Muscle Atrophy in the Intensive Care Unit (STROMA-ICU)
Study Start Date : January 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Arm Intervention/treatment
Placebo Comparator: Placebo + Vital HP
GROUP 1 will receive Placebo (within 24 hours of ICU admission) and Vital HP ® (while on tube feeds). Vital HP® is on the Massachusetts General hospital formulary, but it is often restricted to patients with malabsorption due to its higher cost compared to other standard enteral nutrition formulas.
Dietary Supplement: Placebo
The placebo is cornstarch and will be mixed in with Vital HP. The solution will look identical to the intervention arm.

Dietary Supplement: Vital HP®
Vital HP® is a form of enteral nutrition a part of the Massachusetts General enteral formulary

Experimental: B-hydroxy-B-methylbutyrate (HMB) + Vital HP
GROUP 2 will receive beta-hydroxy-beta-methylbutyrate (within 24 hours of ICU admission) and Vital HP ® (while on tube feeds). Vital HP® is on the Massachusetts General hospital formulary, but it is often restricted to patients with malabsorption due to its higher cost compared to other standard enteral nutrition formulas. The investigators will limit HMB dosing to 3g/day since this is the most widely studied dose.
Dietary Supplement: beta-hydroxy-beta-methylbutyrate
HMB is a leucine metabolite that may also be a potent mediator of anabolic processes in skeletal muscle; subjects will not receive >3g of HMB/ day.
Other Name: HMB

Dietary Supplement: Vital HP®
Vital HP® is a form of enteral nutrition a part of the Massachusetts General enteral formulary




Primary Outcome Measures :
  1. Change in muscle thickness (diaphragm) at 14 days after ICU admission. [ Time Frame: Day 14 of ICU admission or through study completion, an average of 1 month ]
    Change in muscle thickness will be assessed via ultrasound (base line and 14 days)

  2. Change in muscle thickness (quadriceps at 14 days after ICU admission. [ Time Frame: Day 14 of ICU admission or through study completion, an average of 1 month ]
    Change in muscle thickness will be assessed via ultrasound (baseline and 14 days)


Secondary Outcome Measures :
  1. Intensive care unit length of stay [ Time Frame: Time of admission to the ICU until the time of discharge from the intensive care unit, up to 100 weeks ]
  2. Hospital Length of Stay [ Time Frame: Time of discharge from the ICU until hospital discharge, up to 100 weeks ]
  3. 30-day ventilator free days [ Time Frame: number of days during ICU admission not requiring invasive mechanical ventilation support, or until study completion, up to 100 weeks ]
    number of days not requiring invasive mechanical ventilation support

  4. Discharge destination (home vs. non-home) [ Time Frame: time of discharge until 90 days after discharge ]
    Assess where patients as discharged to

  5. 30-day readmission [ Time Frame: From the time of hospital discharge until 30-days after hospitalization ]
    Assess readmission rates in both groups

  6. 30-day all-cause mortality [ Time Frame: From the time of hospital discharge until 30 days after hospitalization ]
    Assess 30 day all cause mortality in both groups



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years or older
  2. English-speaking
  3. Expected to require at least 72 hours of ICU care
  4. Able to provide written/verbal consent or have a suitable healthcare proxy
  5. Able to ultrasound the diaphragm and quadriceps muscles in a consistent location for 7 days
  6. Ability to take study drug orally vs. an indwelling nasogastric, orogastric, gastric, or gastrojejunostomy tube

Exclusion Criteria:

  1. Pregnant or peri-partum female
  2. Baseline hemoglobin less than 8g/dL
  3. Not expected to survive beyond 72 hours
  4. Unable to provide a written/verbal consent or an available healthcare proxy
  5. Enrolled in another study which may interfere with the current study
  6. Prior ICU admission with 1 year of current admission or more than 7 days of hospital admission before transfer to the ICU
  7. Strict "nil per os" (NPO) status
  8. High output through naso/orogastric tube
  9. Clinically significant bowel obstruction
  10. Active cancer (except for actinic keratosis, squamous cell carcinoma, and basal cell carcinoma confined to the skin)
  11. Palliative care status
  12. Known or anticipated history of difficult blood draws
  13. History of elevated low density lipoprotein (LDL) and not on a stable treatment regimen
  14. Blood urea nitrogen (BUN): creatinine >20 without an underlying cause
  15. History of hypoglycemia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02773771


Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Sadeq A. Quraishi, MD,MHA,MMSc Massachusetts General Hospital
Publications:
Baggett B, Bruckbauer A, Zemel M. Synergistic Effects of Leucine and its Metabolites with Polyphenols on Irisin in Myotubes and Diet-induced Obese Mice. FASEB J. 2013;27:637.11.

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Responsible Party: Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02773771    
Other Study ID Numbers: 2016p001044
First Posted: May 16, 2016    Key Record Dates
Last Update Posted: May 5, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Massachusetts General Hospital:
Muscle Atrophy
Critical Illness
Ultrasound
beta-hydroxy-beta-methylbutyrate
ICU
Additional relevant MeSH terms:
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Muscular Atrophy
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases