Liver Disease
Conditions
Keywords
Hepatic Venous Pressure Gradient (HVPG) testing, HepQuant-SHUNT, Liver Function
Brief summary
This study plans to learn more about a new test to look at liver function, the HepQuant-Shunt (HQ-Shunt). The HQ-Shunt is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient testing in patients with liver disease.
Detailed description
The goal of this study is to demonstrate the HQ-SHUNT is safe, simple to administer, noninvasive, cost-effective, and well tolerated by patients. This study will compare the HQ-SHUNT to Hepatic Venous Pressure Gradient (HVPG) testing. In this study, 100 consecutive patients with various etiologies of liver disease who have undergone technically successful HVPG testing as standard of care will also undergo HQ-SHUNT testing.
Interventions
DRUGHepQuant-SHUNT (Drug and Device) #65,123 (4D-cholate) and IND #65,121 (13C-cholate)
The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease
Hepatic Venous Pressure Gradient (HVPG) is a test for patients with liver disease
Sponsors
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Liver disease patient scheduled to have an Hepatic Venous Pressure Gradient (HVPG) procedure * At time of enrollment, being between the ages of 18 and 75
Exclusion criteria
* Concomitant treatment with both a beta blocker and an ACE inhibitor * Concurrent hepatic malignancy. Patients with a history of treated HCC can be included if there is no evidence of recurrent disease at the time of this study. * Unstable angina or history of myocardial infarction or congestive heart failure within 6 months prior to enrollment into this study * Renal insufficiency with chronic kidney disease stage 4 or 5 (GFR \< 30 mL/min/1.73m2) * Crohn's disease or any active intestinal inflammatory condition * Having had an ileal resection * Diabetic Gastroparesis * Pregnancy or intent to become pregnant. Urine pregnancy tests will be performed prior to HQ SHUNT testing. * Inability to consent for one's self
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Results of HepQuant SHUNT Test: STAT | 60 minutes | Compare HepQuant STAT test from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. HepQuant STAT is a simple drink and draw blood-based clearance test that quantifies hepatic impairment from early through late stages of disease. |
| Results of HepQuant SHUNT Test: SHUNT | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. SHUNT% is The percent of the oral dose of cholate that escapes hepatic extraction |
| Results of HepQuant SHUNT Test: DSI Score | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. DSI range is from 0 to 50. 0 implies no disease; 50 implies severe end-stage disease. |
| Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1) | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. |
| Results of HepQuant SHUNT Test: Systemic Clearance | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. Systemic Clearance (13C-CA; ml min-1) |
| Results of HepQuant SHUNT Test: Apparent Portal Clearance | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. |
| Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. |
| Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate | Up to 90 minutes | Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hours for Test | Baseline, up to Day 60 | Number of hours it took for subjects to complete each test |
| Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Immediately post HepQuant SHUNT test (Baseline up to Day 60) | Overall experience and willingness to repeat 0-10 Scale 0 being no pain, 10 being severe pain 0 being no discomfort, 10 being severe discomfort 0 being no interference with daily life, 10 being unable to carry on activities 0 being very negative experience, 10 being very positive experience 0 being definitely not wanting to have the test again, 10 being very willing to have the test again |
Countries
United States
Participant flow
Pre-assignment details
Subjects can be excluded if they do not complete the study visit within 60 days of the HVPG testing or if they test positive in a urine pregnancy test the day of the HQ-SHUNT test.
Participants by arm
| Arm | Count |
|---|---|
| HepQuant-SHUNT (HQ-Shunt) Comparison of Disease Severity Index (DSI) from HQ-SHUNT with HVPG in identifying patients with cirrhosis and patients with varices.
HepQuant-SHUNT: The HQ-SHUNT test is being evaluated for safety and effectiveness as an alternative to Hepatic Venous Pressure Gradient (HVPG) testing in patients with liver disease | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | HepQuant-SHUNT (HQ-Shunt) |
|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 10.1 |
| Co-Morbid Conditions Diabetes Mellitus | 9 participants |
| Co-Morbid Conditions Dyslipidemia | 4 participants |
| Co-Morbid Conditions Extrahepatic autoimmune disease | 7 participants |
| Co-Morbid Conditions Gout | 1 participants |
| Co-Morbid Conditions Hypertension | 8 participants |
| Co-Morbid Conditions Malignancy | 1 participants |
| Co-Morbid Conditions Obesity | 10 participants |
| Co-Morbid Conditions Pulmonary hypertension | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Etiology of Liver Disease Autoimmune Hepatitis | 3 Participants |
| Etiology of Liver Disease Budd-Chiari Syndrome | 1 Participants |
| Etiology of Liver Disease Cryptogenic | 1 Participants |
| Etiology of Liver Disease HCV | 4 Participants |
| Etiology of Liver Disease NASH | 9 Participants |
| Etiology of Liver Disease Other | 1 Participants |
| Etiology of Liver Disease Wilsons Disease | 1 Participants |
| Fibrosis Stage F0 | 2 Participants |
| Fibrosis Stage F1 | 6 Participants |
| Fibrosis Stage F2-F3 (F2.5) | 3 Participants |
| Fibrosis Stage F3 | 3 Participants |
| Fibrosis Stage F4 | 5 Participants |
| Fibrosis Stage NA | 1 Participants |
| Race/Ethnicity, Customized Non-Wihite | 0 Participants |
| Race/Ethnicity, Customized White | 20 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 5 Participants |
| Standard Laboratory Tests: Albumin | 3.79 g/L STANDARD_DEVIATION 0.49 |
| Standard Laboratory Tests: AST, Alkaline Phosphatase, ALT Alkaline Phosphatase | 108 IU/L STANDARD_DEVIATION 100 |
| Standard Laboratory Tests: AST, Alkaline Phosphatase, ALT ALT | 53 IU/L STANDARD_DEVIATION 45 |
| Standard Laboratory Tests: AST, Alkaline Phosphatase, ALT AST | 46 IU/L STANDARD_DEVIATION 36 |
| Standard Laboratory Tests: Child-Turcotte-Pugh (CTP) Score | 5.35 units on a scale STANDARD_DEVIATION 0.59 |
| Standard Laboratory Tests: Creatine, Glucose and Bilirubin Bilirubin | 0.75 mg/dL STANDARD_DEVIATION 0.34 |
| Standard Laboratory Tests: Creatine, Glucose and Bilirubin Creatine | 0.71 mg/dL STANDARD_DEVIATION 0.15 |
| Standard Laboratory Tests: Creatine, Glucose and Bilirubin Glucose | 149 mg/dL STANDARD_DEVIATION 140 |
| Standard Laboratory Tests: Hematocrit | 39.60 % STANDARD_DEVIATION 7.5 |
| Standard Laboratory Tests: Hemoglobin | 13.38 g/dL STANDARD_DEVIATION 2.91 |
| Standard Laboratory Tests: INR | 1.11 No units (ratio) STANDARD_DEVIATION 0.14 |
| Standard Laboratory Tests: MELD Score | 7.35 units on a scale STANDARD_DEVIATION 1.84 |
| Standard Laboratory Tests: Serum Sodium | 136 mEq/L STANDARD_DEVIATION 4 |
| Standard Laboratory Tests: WBC, RBC and Platelets Platelets | 218.45 count/nL STANDARD_DEVIATION 102.56 |
| Standard Laboratory Tests: WBC, RBC and Platelets RBC | 4.44 count/nL STANDARD_DEVIATION 0.84 |
| Standard Laboratory Tests: WBC, RBC and Platelets WBC | 7.22 count/nL STANDARD_DEVIATION 3.06 |
| Steatosis Grade Mild, <5% | 4 Participants |
| Steatosis Grade Mild, 5 to 33% | 9 Participants |
| Steatosis Grade Moderate, 33 to 66% | 4 Participants |
| Steatosis Grade NA | 2 Participants |
| Steatosis Grade Severe, >66% | 1 Participants |
| Weight | 87.1 Kg STANDARD_DEVIATION 19.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Results of HepQuant SHUNT Test: Apparent Portal Clearance
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension.
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: Apparent Portal Clearance | 1538 d4-CA; ml min-1 | Standard Deviation 525 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: Apparent Portal Clearance | 975 d4-CA; ml min-1 | Standard Deviation 464 |
| All Patients | Results of HepQuant SHUNT Test: Apparent Portal Clearance | 1285 d4-CA; ml min-1 | Standard Deviation 564 |
Primary
Results of HepQuant SHUNT Test: DSI Score
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. DSI range is from 0 to 50. 0 implies no disease; 50 implies severe end-stage disease.
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: DSI Score | 14.64 score on a scale (DSI Score) | Standard Deviation 3.86 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: DSI Score | 20.68 score on a scale (DSI Score) | Standard Deviation 6.3 |
| All Patients | Results of HepQuant SHUNT Test: DSI Score | 17.36 score on a scale (DSI Score) | Standard Deviation 5.84 |
Primary
Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1)
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension.
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1) | 0.104 min-1 | Standard Deviation 0.017 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1) | 0.092 min-1 | Standard Deviation 0.023 |
| All Patients | Results of HepQuant SHUNT Test: Elimination Rate (IV Phase 1 Only; Min-1) | 0.099 min-1 | Standard Deviation 0.02 |
Primary
Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension.
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate | 17.83 ml min-1 kg-1 | Standard Deviation 6.37 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate | 11.11 ml min-1 kg-1 | Standard Deviation 5.24 |
| All Patients | Results of HepQuant SHUNT Test: Portal Hepatic Filtration Rate | 14.81 ml min-1 kg-1 | Standard Deviation 6.69 |
Primary
Results of HepQuant SHUNT Test: SHUNT
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. SHUNT% is The percent of the oral dose of cholate that escapes hepatic extraction
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: SHUNT | 29.08 percentage | Standard Deviation 9.89 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: SHUNT | 47.50 percentage | Standard Deviation 24.24 |
| All Patients | Results of HepQuant SHUNT Test: SHUNT | 37.37 percentage | Standard Deviation 19.68 |
Primary
Results of HepQuant SHUNT Test: STAT
Compare HepQuant STAT test from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. HepQuant STAT is a simple drink and draw blood-based clearance test that quantifies hepatic impairment from early through late stages of disease.
Time frame: 60 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: STAT | 0.61 uM/min | Standard Deviation 0.27 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: STAT | 1.29 uM/min | Standard Deviation 0.73 |
| All Patients | Results of HepQuant SHUNT Test: STAT | 0.92 uM/min | Standard Deviation 0.62 |
Primary
Results of HepQuant SHUNT Test: Systemic Clearance
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension. Systemic Clearance (13C-CA; ml min-1)
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: Systemic Clearance | 463 (13C-CA; ml min-1) | Standard Deviation 161 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: Systemic Clearance | 384 (13C-CA; ml min-1) | Standard Deviation 137 |
| All Patients | Results of HepQuant SHUNT Test: Systemic Clearance | 427 (13C-CA; ml min-1) | Standard Deviation 152 |
Primary
Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate
Compare Disease Severity Index (DSI) from HQ-SHUNT for defining patients with (HVPG ≥6 mmHg) and without (HVPG \<6 mmHg) portal hypertension.
Time frame: Up to 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HVPG <6 mmHg | Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate | 5.30 ml min-1 kg-1 | Standard Deviation 1.09 |
| HVPG ≥6 mmHg | Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate | 4.47 ml min-1 kg-1 | Standard Deviation 1.43 |
| All Patients | Results of HepQuant SHUNT Test: Systemic Hepatic Filtration Rate | 4.92 ml min-1 kg-1 | Standard Deviation 1.29 |
Secondary
Hours for Test
Number of hours it took for subjects to complete each test
Time frame: Baseline, up to Day 60
Population: Number of hours
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HVPG <6 mmHg | Hours for Test | 0-3 hours | 4 participants |
| HVPG <6 mmHg | Hours for Test | 3-6 hours | 5 participants |
| HVPG <6 mmHg | Hours for Test | 6-9 hours | 3 participants |
| HVPG <6 mmHg | Hours for Test | 9-12 hours | 8 participants |
| HVPG ≥6 mmHg | Hours for Test | 9-12 hours | 0 participants |
| HVPG ≥6 mmHg | Hours for Test | 0-3 hours | 18 participants |
| HVPG ≥6 mmHg | Hours for Test | 6-9 hours | 0 participants |
| HVPG ≥6 mmHg | Hours for Test | 3-6 hours | 2 participants |
Secondary
Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures.
Overall experience and willingness to repeat 0-10 Scale 0 being no pain, 10 being severe pain 0 being no discomfort, 10 being severe discomfort 0 being no interference with daily life, 10 being unable to carry on activities 0 being very negative experience, 10 being very positive experience 0 being definitely not wanting to have the test again, 10 being very willing to have the test again
Time frame: Immediately post HepQuant SHUNT test (Baseline up to Day 60)
Population: subjects that underwent HVPG and HQ-Shunt completed surveys
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HVPG <6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Discomfort | 4.2 units on a scale | Standard Deviation 2.89 |
| HVPG <6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Overall Experience | 6.2 units on a scale | Standard Deviation 2.73 |
| HVPG <6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Interfere with Daily Life | 5.9 units on a scale | Standard Deviation 3.14 |
| HVPG <6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Willingness to Repeat | 5.65 units on a scale | Standard Deviation 3.59 |
| HVPG <6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Pain | 3.9 units on a scale | Standard Deviation 3.14 |
| HVPG ≥6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Willingness to Repeat | 9.85 units on a scale | Standard Deviation 0.37 |
| HVPG ≥6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Pain | .35 units on a scale | Standard Deviation 0.59 |
| HVPG ≥6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Discomfort | .5 units on a scale | Standard Deviation 0.89 |
| HVPG ≥6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Interfere with Daily Life | 1.25 units on a scale | Standard Deviation 1.41 |
| HVPG ≥6 mmHg | Survey Patients on Their Experience of Having Both HQ-SHUNT and HVPG Procedures. | Overall Experience | 9.6 units on a scale | Standard Deviation 0.68 |