Muscle Weakness, Sepsis
Conditions
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.
Interventions
DRUGLorcaserin
10 mg, oral or enteral, single dose. 30 mg, oral or enteral, single dose two days later
DRUGPlacebo
Oral or enteral, single dose. Oral or enteral, single dose two days later
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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). |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention 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 | 3 |
| Control 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 | 2 |
| Total | 5 |
Baseline characteristics
| Characteristic | Intervention | Total | Control |
|---|---|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 19.8 | 60.6 years STANDARD_DEVIATION 17.2 | 56.0 years STANDARD_DEVIATION 18.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 1 Participants |
| Region of Enrollment United States | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
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)
Time frame: Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Handgrip Strength as Measured by Hand Dynamometer | 0.67 percent of predicted strength | Standard Deviation 2.93 |
| Control | Change in Handgrip Strength as Measured by Hand Dynamometer | 1.75 percent of predicted strength | Standard Deviation 1.06 |
Secondary
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)
Time frame: Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Handgrip Strength as Measured by Hand Dynamometer | -3.83 percent of predicted strength | Standard Deviation 1.89 |
| Control | Change in Handgrip Strength as Measured by Hand Dynamometer | 2.25 percent of predicted strength | Standard Deviation 0.35 |
Secondary
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).
Time frame: Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score | 1.00 score on a scale | Standard Deviation 1.73 |
| Control | Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score | 0.50 score on a scale | Standard Deviation 0.71 |
Secondary
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).
Time frame: Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score | 0.33 score on a scale | Standard Deviation 3.5 |
| Control | Change in Manual Muscle Strength as Measured by the Medical Research Council (MRC) Score | 3.50 score on a scale | Standard Deviation 2.12 |
Secondary
Change in Quadriceps Strength as Measured by Handheld Dynamometer
Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.
Time frame: Baseline and 2 to 6 hours after administration of 30mg lorcaserin/placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Quadriceps Strength as Measured by Handheld Dynamometer | -0.23 kilograms | Standard Deviation 1.83 |
| Control | Change in Quadriceps Strength as Measured by Handheld Dynamometer | 4.15 kilograms | Standard Deviation 2.19 |
Secondary
Change in Quadriceps Strength as Measured by Handheld Dynamometer
Strength (in kilograms) - measured via handheld dynamometry of quadriceps muscle.
Time frame: Baseline and 2 to 6 hours after administration of 10mg lorcaserin/placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Quadriceps Strength as Measured by Handheld Dynamometer | 0.02 kilograms | Standard Deviation 1.23 |
| Control | Change in Quadriceps Strength as Measured by Handheld Dynamometer | 2.13 kilograms | Standard Deviation 5.76 |