Evaluating Muscle Weakness Improvement With Lorcaserin in ICU

Study Overview
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Brief Summary
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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.

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

Conditions
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Muscle Weakness, Sepsis

Intervention / Treatment
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* Drug: Lorcaserin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |