EMILI: Evaluating Muscle Weakness Improvement With Lorcaserin in ICU

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02523690
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Actual Duration (Months): 24
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Muscle Weakness; Sepsis	Drug: Lorcaserin; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluating Lorcaserin Drug Therapy For ICU-Acquired Weakness: A Pilot Randomized Trial
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Handgrip Strength as Measured by Hand Dynamometer [Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo]

   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)

Secondary Outcome Measures

1. Change in Handgrip Strength as Measured by Hand Dynamometer [Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo]

   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)

2. Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score [Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo]

   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).

3. Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score [Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo]

   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).

4. Change in Quadriceps Strength as Measured by Handheld Dynamometer [Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo]

   Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.

5. Change in Quadriceps Strength as Measured by Handheld Dynamometer [Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo]

   Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Johns Hopkins University

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 10, 2017

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02523690
• Other Study ID Numbers: IRB00072940; UL1TR001079
• First Posted: Aug 14, 2015
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Muscle Weakness; Paresis; Asthenia

Study Results

Participant Flow

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Period Title: Overall Study
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intervention	Control	Total
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later	Total of all reporting groups
Overall Participants	3	2	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.7 (19.8)	56.0 (18.4)	60.6 (17.2)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	1 50%	3 60%
Male	1 33.3%	1 50%	2 40%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 50%	1 20%
White	3 100%	1 50%	4 80%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%	2 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Change in Handgrip Strength as Measured by Hand Dynamometer
Description	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)
Time Frame	Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Measure Participants	3	2
Mean (Standard Deviation) [percent of predicted strength]	0.67 (2.93)	1.75 (1.06)

2. Secondary Outcome

Title	Change in Handgrip Strength as Measured by Hand Dynamometer
Description	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)
Time Frame	Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Measure Participants	3	2
Mean (Standard Deviation) [percent of predicted strength]	-3.83 (1.89)	2.25 (0.35)

3. Secondary Outcome

Title	Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score
Description	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).
Time Frame	Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Measure Participants	3	2
Mean (Standard Deviation) [score on a scale]	0.33 (3.5)	3.50 (2.12)

4. Secondary Outcome

Title	Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score
Description	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).
Time Frame	Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Measure Participants	3	2
Mean (Standard Deviation) [score on a scale]	1.00 (1.73)	0.50 (0.71)

5. Secondary Outcome

Title	Change in Quadriceps Strength as Measured by Handheld Dynamometer
Description	Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.
Time Frame	Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Measure Participants	3	2
Mean (Standard Deviation) [kilograms]	-0.23 (1.83)	4.15 (2.19)

6. Secondary Outcome

Title	Change in Quadriceps Strength as Measured by Handheld Dynamometer
Description	Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.
Time Frame	Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later	Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
Measure Participants	3	2
Mean (Standard Deviation) [kilograms]	0.02 (1.23)	2.13 (5.76)

Adverse Events

Time Frame	While admitted in hospital. For the 5 participants in this study, the mean number of days between enrollment and hospital discharge is 17.6 days (standard deviation 12.9 days)
Arm/Group Title	Intervention		Control
Arm/Group Description	Lorcaserin will be administered as a single dose on day 1 and day 3 to participants in this arm. Lorcaserin: 10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later		Placebo will be administered as a single dose on day 1 and day 3 to participants in this arm. Placebo: Oral or enteral, single dose. Oral or enteral, single dose two days later
All Cause Mortality
	Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Serious Adverse Events
	Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/03 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.