Fatty LiverPhase 1NCT01766960
Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease
A Phase 1 study testing High fat meal and Morphine in people with Fatty Liver, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
One-third of the U.S. population suffers from non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by diabetes and obesity, and is becoming more common. Although many people have this disease, the change in how the liver handles drugs and compounds in the body has not been studied. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Fatty Liver
- What is being tested?
- High fat meal and Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Jun 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General:
- Man or woman between 18 and 65 years of age
- Negative pregnancy test for women of childbearing potential
- Negative urine drug screen
- Healthy Subjects:
- Normal liver function tests
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- Normal kidney function and lipid panel
- Nonalcoholic Steatohepatitis Patients:
- Recent liver biopsy with nonalcoholic fatty liver disease activity score at least 4
Who cannot join
- General:
- History of significant alcohol use (>20 g/day) and/or illicit drug use
- Inability to abstain from alcohol for 48 prior to study
- Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens (at doses greater than those used for hormone replacement) or valproate/valproic acid
- Type 2 diabetes treated with oral agents other than metformin; these include secretagogues, thiazolidinediones, alpha-glucosidase inhibitors, exenatide and pramlintide.
- Current or recent use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives.
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- Current use of antioxidants such as silymarin, vitamin C, glutathione, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening.
- Previous liver biopsy that demonstrated presence of cirrhosis.
- Radiologic imaging consistent with cirrhosis or portal hypertension.
- Serum creatinine of 2.0 mg/dL or greater, or on dialysis, at screening.
- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect the assessment of biomarkers (bile acids or inflammation).
- History of bariatric surgery.
- BMI > 45 kg/m^2 at screening.
- Any known hypersensitivity to opiates, opiate antagonists, or ondansetron.
- Healthy Subjects:
- Taking concomitant medications, both prescription and non-prescription (including herbal products and over-the-counter medications), other than oral contraceptives and multivitamins (women stabilized on hormonal methods of birth control will be allowed to participate)
- History or other evidence of liver disease in the opinion of the study investigators.
- BMI > 30 kg/m^2 at screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
North Carolina Clinical and Translational Research Center
Chapel Hill, North Carolina, 27599
About this study
Official title: Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease.
One-third of the U.S. population suffers from non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by diabetes and obesity, and is becoming more common. Although many people have this disease, the change in how the liver handles drugs and compounds in the body has not been studied. The purpose of this study is to investigate how advanced NAFLD changes the ability of the liver to handle both endogenous and exogenous compounds.
- Conditions
- Fatty Liver
- Being tested
- High fat meal, Morphine
- Keywords
- Bile acids, Pharmacokinetics
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High fat mealOther
A high fat breakfast will be administered to induce gall bladder emptying.
MorphineDrug
Five milligrams of intravenous morphine will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers | Experimental | Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours. Receives: Other: High fat meal; Drug: Morphine |
| Advanced nonalcoholic fatty liver disease patients | Experimental | Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours. Receives: Other: High fat meal; Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic profile of morphine and its hepatically derived metabolites.
Morphine will be administered as a 5-min IV infusion. Pharmacokinetic profiles of morphine and morphine metabolites will be quantified in the serum over the 8-hour sampling period. Non-compartmental analysis will be performed using Pharsight Phoenix software, comparing the following parameters between healthy subjects and patients with advanced NAFLD. The maximal concentration, time of maximal concentration, elimination half-life, area under the curve, and systemic and renal clearances will be calculated for both morphine and the glucuronide metabolites. Volume of distribution and metabolic clearance will be calculated for morphine.
Measured: 8 hours post dose
Secondary outcomes (2)
Bile acid profile
The bile acid profile in healthy and diseased subjects will be assessed following an 8 hour fast and every 30 min for 2 hours following a high fat breakfast. At each of the 5 time points, serum concentrations of total and selected individual bile acid species will be quantified and compared between healthy subjects and patients with advanced NAFLD. Comparison of the bile acid profile, comprised of all selected bile acids, between subjects and patients will pose as the primary endpoint for this outcome.
Measured: Pre- and postprandially
FibroScan with Controlled Attenuation Parameter (CAP) Software
FibroScan is more sensitive method to identify less severe scarring of liver tissue when compared to liver ultrasound and contrary to liver biopsy, it is not invasive. In this study, Fibroscan will be used to assess the extent of liver fibrosis in both healthy volunteers and patients diagnosed with NAFLD and the CAP software will be used to estimate fat liver content. These findings will be correlated with changes in morphine disposition and bile acid profile observed in the study participants as described above.
Measured: No preparation (fasting) required-consumption of large meals prior to the Fibroscan procedure is not advised
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2013 (estimated)
- Study startNov 2012
- Primary completionMar 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fatty LiverStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- University of North Carolina, Greensboro
- Responsible party
- Principal investigator, Sidney Barritt, MD, University of North Carolina, Chapel Hill
- Investigators
- Alfred S Barritt, MD, Principal investigator, University of North Carolina, Chapel HillKim LR Brouwer, PharmD, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01766960
- Sponsor's protocol ID
- 12-1599
- Other IDs
- 550KR41202
- Status last verified
- Mar 2016
- First submitted
- 4 Jan 2013
- Last updated
- 3 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease.
- ClinicalTrials.gov ID
- NCT01766960
- Acronym / sponsor ID
- 12-1599
- Conditions
- Fatty Liver
- Keywords
- Bile acids, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- University of North Carolina, Greensboro
- Study start
- Nov 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 11 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One-third of the U.S. population suffers from non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by diabetes and obesity, and is becoming more common. Although many people have this disease, the change in how the liver handles drugs and compounds in the body has not been studied. The purpose of this study is to investigate how advanced NAFLD changes the ability of the liver to handle both endogenous and exogenous compounds.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | Experimental | Other: High fat meal, Drug: MorphineSubjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours. |
| Advanced nonalcoholic fatty liver disease patients | Experimental | Other: High fat meal, Drug: MorphineSubjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Man or woman between 18 and 65 years of age
- Negative pregnancy test for women of childbearing potential
- Negative urine drug screen
- Normal liver function tests
- Normal kidney function and lipid panel
Key exclusion criteria (18 listed)
- History of significant alcohol use (>20 g/day) and/or illicit drug use
- Inability to abstain from alcohol for 48 prior to study
- Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens (at doses greater than those used for hormone replacement) or valproate/valproic acid
- Type 2 diabetes treated with oral agents other than metformin; these include secretagogues, thiazolidinediones, alpha-glucosidase inhibitors, exenatide and pramlintide.
- Current or recent use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High fat mealA high fat breakfast will be administered to induce gall bladder emptying. | Other | Advanced nonalcoholic fatty liver disease patients, Healthy volunteers |
| MorphineFive milligrams of intravenous morphine will be administered. | Drug | Advanced nonalcoholic fatty liver disease patients, Healthy volunteers |
Primary outcome
Pharmacokinetic profile of morphine and its hepatically derived metabolites.
Time frame: 8 hours post dose
Morphine will be administered as a 5-min IV infusion. Pharmacokinetic profiles of morphine and morphine metabolites will be quantified in the serum over the 8-hour sampling period. Non-compartmental analysis will be performed using Pharsight Phoenix software, comparing the following parameters between healthy subjects and patients with advanced NAFLD. The maximal concentration, time of maximal concentration, elimination half-life, area under the curve, and systemic and renal clearances will be calculated for both morphine and the glucuronide metabolites. Volume of distribution and metabolic clearance will be calculated for morphine.
2 secondary outcomes
Bile acid profile
Time frame: Pre- and postprandially
FibroScan with Controlled Attenuation Parameter (CAP) Software
Time frame: No preparation (fasting) required-consumption of large meals prior to the Fibroscan procedure is not advised
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfred S Barritt, MD principal investigator
University of North Carolina, Chapel Hill
Kim LR Brouwer, PharmD, PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing High fat meal and Morphine in people with Fatty Liver, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic profile of morphine and its hepatically derived metabolites. (time frame: 8 hours post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2016.