Strategies to Reduce Organic Muscle Atrophy in the Intensive Care Unit

NCT02773771 | Withdrawn Phase 2

• 1 other identifier: 2016p001044
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Muscle Atrophy

Keywords

Muscle Atrophy; Critical Illness; Ultrasound; beta-hydroxy-beta-methylbutyrate; ICU

Outcome Measures

Primary Outcomes (2)

• Change in muscle thickness (diaphragm) at 14 days after ICU admission.

  Change in muscle thickness will be assessed via ultrasound (base line and 14 days)

  Day 14 of ICU admission or through study completion, an average of 1 month

• Change in muscle thickness (quadriceps at 14 days after ICU admission.

  Change in muscle thickness will be assessed via ultrasound (baseline and 14 days)

  Day 14 of ICU admission or through study completion, an average of 1 month

Secondary Outcomes (6)

• Intensive care unit length of stay

  Time of admission to the ICU until the time of discharge from the intensive care unit, up to 100 weeks

• Hospital Length of Stay

  Time of discharge from the ICU until hospital discharge, up to 100 weeks

• 30-day ventilator free days

  number of days during ICU admission not requiring invasive mechanical ventilation support, or until study completion, up to 100 weeks

• Discharge destination (home vs. non-home)

  time of discharge until 90 days after discharge

• 30-day readmission

  From the time of hospital discharge until 30-days after hospitalization

Study Arms (2)

Placebo + Vital HP

PLACEBO COMPARATOR

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; Dietary Supplement: Vital HP®

B-hydroxy-B-methylbutyrate (HMB) + Vital HP

EXPERIMENTAL

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; Dietary Supplement: Vital HP®

Interventions

beta-hydroxy-beta-methylbutyrate DIETARY_SUPPLEMENT

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.

Also known as: HMB

B-hydroxy-B-methylbutyrate (HMB) + Vital HP

Placebo DIETARY_SUPPLEMENT

The placebo is cornstarch and will be mixed in with Vital HP. The solution will look identical to the intervention arm.

Placebo + Vital HP

Vital HP® DIETARY_SUPPLEMENT

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

B-hydroxy-B-methylbutyrate (HMB) + Vital HP; Placebo + Vital HP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

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MeSH Terms

Conditions

Muscular Atrophy; Critical Illness

Interventions

beta-hydroxyisovaleric acid

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Disease Attributes; Pathologic Processes

Study Officials

• Sadeq A. Quraishi, MD,MHA,MMSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2016
• First Posted: May 16, 2016
• Study Start: January 1, 2017
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: May 5, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share