Evaluating Muscle Weakness Improvement With Lorcaserin in ICU (EMILI)

Evaluating Lorcaserin Drug Therapy For ICU-Acquired Weakness: A Pilot Randomized Trial

ICU acquired muscle weakness is a significant problem in patients recovering from critical illness. This trial will evaluate the safety and efficacy of a drug in improving muscle weakness in critically ill patients.

Study Overview

• Status: Terminated
• Conditions: Sepsis; Muscle Weakness
• Intervention / Treatment: Drug: Lorcaserin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years old
• Sepsis [ ≥2 Systemic Inflammatory Response Syndrome (SIRS) Criteria AND known or suspected infection]
• Muscle weakness [Medical Research Council sum score <48/60 or handgrip strength <11 kg in men and <7 kg in women]
• Obey Commands [Score for DeJonghe Awakening Score of ≥3/5]

Exclusion Criteria:

• Severe renal insufficiency [Creatinine Clearance <30 mL/min - or receiving dialysis]
• Acute infectious or auto-immune hepatitis, acute liver failure or a history of cirrhosis without liver transplant
• History of psychosis
• Bradycardia, or 2nd or 3rd degree Atrio-Ventricular block without pacemaker
• History of valvular heart disease without valve replacement
• History of priapism
• Pre-existing cognitive impairment
• Receiving drugs with serotonergic effects and/or CYP2D6 substrates which cannot be substituted stopped or titrated.
• Receiving Sulfonylurea medication at the time of the study
• Prior neuromuscular or central nervous system disease, including pre-existing neuropathy
• Inability to perform study's muscle strength assessments based on patient's baseline status prior to hospital admission
• Unable to receive, or unlikely to absorb study drug (e.g. bowel obstruction, ischemia, or infarction; short gut syndrome)
• Body mass index >40
• Patient not expected to survive >4 days
• Pregnancy or lactation
• Allergy to lorcaserin or lorcaserin taken in the prior 7 days
• Enrolled in another interventional drug or physical rehabilitation trial
• Physician declines for patient to be enrolled
• Patient or proxy declines consent
• Unable to reach proxy for consent
• Non-English speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm.	Drug: Lorcaserin; 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later
Placebo Comparator: Control; Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm.	Drug: Placebo; Oral or enteral, single dose. Oral or enteral, single dose two days later

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Handgrip Strength as Measured by Hand Dynamometer	Hand grip strength measured using a dynamometer (measured in kilograms, then compared to age- and sex-matched population norms to yield percent predicted strength - higher is better)	Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Handgrip Strength as Measured by Hand Dynamometer	Hand grip strength measured using a dynamometer (measured in kilograms, then compared to age- and sex-matched population norms to yield percent predicted strength - higher is better)	Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo
Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score	Measuring strength of 6 muscle groups in arms and legs using Medical Research Council composite score (each muscle group scored from scale of 0 [no visible or noticeable contraction] to 5 [maximum strength] and the sum of the scores for the 6 muscle groups equate to a composite score ranging from 0 to 60, higher score is better).	Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo
Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score	Measuring strength of 6 muscle groups in arms and legs using Medical Research Council composite score (each muscle group scored from scale of 0 [no visible or noticeable contraction] to 5 [maximum strength] and the sum of the scores for the 6 muscle groups equate to a composite score ranging from 0 to 60, higher score is better).	Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo
Change in Quadriceps Strength as Measured by Handheld Dynamometer	Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.	Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo
Change in Quadriceps Strength as Measured by Handheld Dynamometer	Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.	Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Dale M Needham, MD, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: August 11, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: December 26, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Paresis; Asthenia
• Other Study ID Numbers: IRB00072940; UL1TR001079 (U.S. NIH Grant/Contract)