Cirrhosis
Conditions
Keywords
Hepatic Encephalopathy, Liver Disease, Cirrhosis and portal hypertension
Brief summary
This trial is being completed to evaluate whether a crystallized form of lactulose (Kristalose) will improve quality of life, sleep and cognitive function in patients with cirrhosis that have not been diagnosed with Hepatic Encephalopathy (HE), but report reduced quality of life.
Interventions
DRUGLactulose
Participants will take 20 grams (dissolved in 4ounces of water/beverage) doses of lactulose twice daily (upon awakening and then 4 hours later) for 28 days. In addition, outcome measurements will be completed at baseline and day 28.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of cirrhosis - must meet one of the following criteria: 1. liver biopsy, OR 2. history of cirrhosis complication: ascites, variceal bleeding, hepatic encephalopathy, OR 3. 2 of the following 4 criteria: 1. Ultrasound, Computed tomography (CT) or Magnetic resonance imaging (MRI) findings of cirrhosis (cirrhotic appearing liver, splenomegaly, varices, ascites) 2. Fibroscan liver stiffness score \>13 Kilopascal (kPa) 3. Laboratory testing: aspartate aminotransferase (AST)/platelet ratio index (APRI) \>2.0 4. CT, MRI or Esophagogastroduodenoscopy (EGD) showing presence of esophageal varices
Exclusion criteria
* Non-English speaking * Pregnancy (self-reported) * Unable or unwilling to provide consent * History of liver transplant * Disorientation at the time of enrollment, Dementia, or Treated Memory Disorder * History of prior lactulose use or HE within 6 months * Metastatic solid malignancy or blood malignancy * Hemoglobin A1C \> 12 (within past year)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Form-8 Health Survey (SF-8) at 28 Days | 28 days | The SF-8 is an abbreviated version of an original 36-item health survey (SF-36). It is a generic, multipurpose, quality of life instrument, containing psychometrically based physical and mental health summary measures. The eight domains are general health, physical functioning, role physical, bodily pain, vitality, social functioning, mental health, and role emotional. Scores from the domains are combined and range from 0 (lowest quality of living) to 100 (highest quality of living). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Animal Naming Test (ANT) | 28 days | Number of unique animals named within 1 minute by the participant. Values below show the change from baseline and the results from the test taken 28 days later. |
| Change in Overall Sleep Quality | Change between baseline (day 0) and 28 days | Overall sleep quality was measured on a 5-point Likert scale, with a range of 1 (very bad sleep quality) to 5 (very good sleep quality). |
| Regular Daily Activity Impairment | 28 days | Single-question survey given to participants at baseline and again 28 days later. Participants ranked their daily activity impairment on a Likert scale of 0 (no impairment) to 10 (complete impairment) |
| Participants Who Fell | 28 days | Yes or no question on whether participant had experienced at least 1 fall in the past 28 days. |
| Daily Bowel Movements | 28 days | Results show the percentage of days in a 28-day span in which participants experienced more than 5 daily bowel movements. All participants analyzed in each arm were included in calculating the results using the following formula: (days with \>5 bowel movements) / (patient-days in study) The results are presented as a single number because they are a point estimate of a population level proportion |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lactulose Lactulose: Participants will take 20 grams (dissolved in 4ounces of water/beverage) doses of lactulose twice daily (upon awakening and then 4 hours later) for 28 days.
In addition, outcome measurements will be completed at baseline and day 28. | 28 |
| No Treatment Subjects will complete baseline and outcome assessments at 28 days and no intervention or placebo will be prescribed. | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Complications of Medical Care | 1 | 0 |
| Overall Study | Diarrhea Prior to Starting Therapy | 1 | 0 |
| Overall Study | Excess bowel movements | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Lactulose | No Treatment |
|---|---|---|---|
| Activity Impairment | 5.6 Score on a Scale STANDARD_DEVIATION 2.1 | 5.4 Score on a Scale STANDARD_DEVIATION 1.9 | 5.7 Score on a Scale STANDARD_DEVIATION 2.1 |
| Age, Continuous | 60.0 years STANDARD_DEVIATION 11.5 | 58.1 years STANDARD_DEVIATION 11.9 | 61.8 years STANDARD_DEVIATION 11.3 |
| Animal Naming Test | 18.1 Count of Animals Named STANDARD_DEVIATION 5.8 | 17.9 Count of Animals Named STANDARD_DEVIATION 5.3 | 18.3 Count of Animals Named STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 28 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Participants Who Fell in Past 90 Days | 7 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 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 | 53 Participants | 27 Participants | 26 Participants |
| Region of Enrollment United States | 56 Participants | 28 Participants | 28 Participants |
| Sex: Female, Male Female | 30 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 26 Participants | 13 Participants | 13 Participants |
| Short Form-8 Health Survey (SF-8) | 59.2 score on a scale STANDARD_DEVIATION 17.7 | 57.2 score on a scale STANDARD_DEVIATION 18.3 | 61.1 score on a scale STANDARD_DEVIATION 17 |
| Sleep Quality | 2.5 Score on a Scale STANDARD_DEVIATION 0.8 | 2.5 Score on a Scale STANDARD_DEVIATION 0.8 | 2.5 Score on a Scale STANDARD_DEVIATION 0.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 1 / 28 | 3 / 28 |
| serious Total, serious adverse events | 1 / 28 | 1 / 28 |
Outcome results
Primary
Short Form-8 Health Survey (SF-8) at 28 Days
The SF-8 is an abbreviated version of an original 36-item health survey (SF-36). It is a generic, multipurpose, quality of life instrument, containing psychometrically based physical and mental health summary measures. The eight domains are general health, physical functioning, role physical, bodily pain, vitality, social functioning, mental health, and role emotional. Scores from the domains are combined and range from 0 (lowest quality of living) to 100 (highest quality of living).
Time frame: 28 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lactulose | Short Form-8 Health Survey (SF-8) at 28 Days | Change in SF-8 from Baseline | 8.1 score on a scale |
| Lactulose | Short Form-8 Health Survey (SF-8) at 28 Days | End of Trial SF-8 | 70.9 score on a scale |
| No Treatment | Short Form-8 Health Survey (SF-8) at 28 Days | Change in SF-8 from Baseline | 6.55 score on a scale |
| No Treatment | Short Form-8 Health Survey (SF-8) at 28 Days | End of Trial SF-8 | 63.84 score on a scale |
Comparison: Change in SF-8p-value: 0.6ANCOVA
Comparison: End of trial SF-8p-value: 0.2ANCOVA
Secondary
Animal Naming Test (ANT)
Number of unique animals named within 1 minute by the participant. Values below show the change from baseline and the results from the test taken 28 days later.
Time frame: 28 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lactulose | Animal Naming Test (ANT) | Change in ANT | 3.7 Count of Animals Named |
| Lactulose | Animal Naming Test (ANT) | End of trial ANT | 21.2 Count of Animals Named |
| No Treatment | Animal Naming Test (ANT) | Change in ANT | -0.15 Count of Animals Named |
| No Treatment | Animal Naming Test (ANT) | End of trial ANT | 18.52 Count of Animals Named |
Comparison: Change in ANTp-value: 0.001ANCOVA
Comparison: End of trial ANTp-value: 0.09t-test, 2 sided
Secondary
Change in Overall Sleep Quality
Overall sleep quality was measured on a 5-point Likert scale, with a range of 1 (very bad sleep quality) to 5 (very good sleep quality).
Time frame: Change between baseline (day 0) and 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactulose | Change in Overall Sleep Quality | 0.4 score on a scale |
| No Treatment | Change in Overall Sleep Quality | 0.0 score on a scale |
p-value: 0.05ANCOVA
Secondary
Daily Bowel Movements
Results show the percentage of days in a 28-day span in which participants experienced more than 5 daily bowel movements. All participants analyzed in each arm were included in calculating the results using the following formula: (days with \>5 bowel movements) / (patient-days in study) The results are presented as a single number because they are a point estimate of a population level proportion
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactulose | Daily Bowel Movements | 5 % of participant-days with >5 bowels |
| No Treatment | Daily Bowel Movements | 2 % of participant-days with >5 bowels |
p-value: 0.2t-test, 2 sided
Secondary
Participants Who Fell
Yes or no question on whether participant had experienced at least 1 fall in the past 28 days.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lactulose | Participants Who Fell | 1 Participants |
| No Treatment | Participants Who Fell | 3 Participants |
p-value: 0.6Fisher Exact
Secondary
Regular Daily Activity Impairment
Single-question survey given to participants at baseline and again 28 days later. Participants ranked their daily activity impairment on a Likert scale of 0 (no impairment) to 10 (complete impairment)
Time frame: 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lactulose | Regular Daily Activity Impairment | 3.0 score on a scale |
| No Treatment | Regular Daily Activity Impairment | 4.8 score on a scale |
p-value: 0.02ANCOVA