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Non-alcoholic SteatohepatitisPhase 1NCT02235233

Effect of Non-Alcoholic Steatohepatitis (NASH) on the Pharmacokinetics of 99mTechnetium-Mebrofenin

A Phase 1 study testing Technetium Tc 99M Mebrofenin in people with Non-alcoholic Steatohepatitis, run by University of North Carolina, Chapel Hill at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is designed to investigate the effect of NASH (non-alcoholic steatohepatitis) on the disposition of 99mTechnetium(Tc)-mebrofenin and to relate changes in 99mTc-mebrofenin disposition to differences in the bile acid profile and Fibroscan Fibrosis Score of healthy subjects compared to patients with NASH. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Non-alcoholic Steatohepatitis
What is being tested?
Technetium Tc 99M Mebrofenin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
Apr 2015to Jul 2016
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

  • Healthy subjects: defined as being free from significant cardiac, pulmonary, gastrointestinal, hepatic, biliary, renal, hematological, neurological and psychiatric disease as determined by history, physical examination and clinical laboratory test results.
  • NASH subjects only: defined as those who have had a recent liver biopsy consistent with NASH without cirrhosis; NAS score >3.
  • Fluent and literate in English.
  • Willing and able to give informed consent prior to entering the study.

Who cannot join

  • Donation of blood within last 30 days.
  • History of significant alcohol abuse (>20g/day) and/or illicit drug use, whether successfully treated or not.
  • Inability to abstain from alcohol for 48 hours prior to study visits.
  • Inability to fast for 8 hours prior to study sample collection.
  • Women who are pregnant, trying to become pregnant, or breast feeding.
  • 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
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  • 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.
  • Serum blood glucose reading at study enrollment of >200 mg/dL.
  • 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. A multivitamin and vitamin E at standard doses will be allowed.
  • Previous liver biopsy that demonstrated presence of cirrhosis.
  • Radiologic imaging consistent with cirrhosis or portal hypertension.
  • Evidence of decompensated liver disease defined as any of the following: serum albumin <3.2 g/dL, total bilirubin > 1.5 mg/dL, or PT/INR > 1.3 times normal at screening, or history or presence of ascites, encephalopathy, or bleeding from esophageal varices.
  • 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).
  • Primary, secondary or extrahepatic malignancy.
  • History of bariatric surgery.
  • Participation in a research drug trial, exclusive of the SyNCH Phase I or II trials, within 30 days of screening.
  • BMI > 45 kg/m2 at screening (body weight is not within 20% of ideal body weight).
  • Inability or unwillingness to give informed consent or abide by the study protocol.
  • Estimated weekly strenuous exercise greater than 4 hours per week.
  • History or other evidence of illness or any other conditions or drug therapies that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, active gastrointestinal conditions or taking drugs known to interfere with bile acid synthesis or metabolism or the metabolism/transport of other drugs).
  • Undergone a radiographic procedure (other than dental X-rays), received radioactive substances, or handled radioactive materials in conjunction with employment within the last twelve months.
  • A history of hypersensitivity to 99mTc-mebrofenin, ultrasound gel, dairy products, or their excipients.
  • Consumed caffeine (coffee, tea, colas, and chocolate) within 24 hours of the study.
  • A history of tobacco use within 12 months of the study.
  • Serology positive for Hepatitis B, Hepatitis C or HIV at screening.
  • A history of any gastrointestinal or hepatobiliary surgery or disorder.
  • Healthy Subjects:
  • Taking concomitant medications, either 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/m2 at screening

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UNC Hospitals

    Chapel Hill, North Carolina, 27514

Other trials in United States

About this study

Official title: Clinical Study to Investigate the Effect of NASH (Non-alcoholic Steatohepatitis) on the Disposition of 99mTechnetium(Tc)-Mebrofenin in Healthy Subjects Compared to Patients With NASH.

This study is designed to investigate the effect of NASH (non-alcoholic steatohepatitis) on the disposition of 99mTechnetium(Tc)-mebrofenin and to relate changes in 99mTc-mebrofenin disposition to differences in the bile acid profile and Fibroscan Fibrosis Score of healthy subjects compared to patients with NASH.

Read the detailed description

This will be an open-label, clinical study in male and female patients with NASH (n=10) and healthy volunteers (n=10) of any race and ethnicity investigating the effect of liver disease on the pharmacokinetics of 99mTechnetium-mebrofenin. The use of the gamma emitter 99m Tc- labeled mebrofenin will allow real-time assessment of hepatic exposure. To determine the differences between healthy subjects and patients with NASH, blood and hepatic concentrations will be analyzed by non-compartmental analysis. Additionally, serum bile acid samples and fibroscan data will be collected to determine whether the bile acid profile and/or fibroscan readings are different between healthy subjects and patients with NASH. Changes in 99mTc-mebrofenin will be correlated with the patient specific bile acid profile and fibroscan data. This study will increase our understating of the effect of liver disease on the disposition of medications that undergo transporter-mediated hepatic clearance.

Being tested
Technetium Tc 99M Mebrofenin
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Technetium Tc 99M MebrofeninDrug

    Also called Choletec

    Each subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin

Study groups in NCT02235233
Study groupRoleWhat they receive
Patients with NASHExperimentalEach subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin
Receives: Drug: Technetium Tc 99M Mebrofenin
Healthy Normal VolunteersActive comparatorEach subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin
Receives: Drug: Technetium Tc 99M Mebrofenin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hepatic exposure (AUC0→∞)

    Area under the hepatic concentration-time curve

    Measured: 0-180 minutes

Secondary outcomes (6)

  1. Systemic exposure (AUC0 →∞)

    Area under the systemic concentration-time curve

    Measured: 0-300 minutes

  2. Cmax (hepatic)

    Peak mebrofenin concentration in the liver

    Measured: 0-180 minutes

  3. Tmax (hepatic)

    Time to peak concentration of mebrofenin in the liver

    Measured: 0-180 minutes

  4. Xurine

    Mass excreted in urine

    Measured: 0-180 minutes

  5. CLuptake

    Hepatic uptake clearance

    Measured: 0-180 minutes

  6. CLrenal

    Renal clearance

    Measured: 0-180 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2014 (estimated)
  2. Study startApr 2015
  3. Primary completionJul 2016
  4. Study completionJul 2016

Resources

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
Basic science
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02235233
Sponsor's protocol ID
13-3362
Other IDs
2R01GM041935
Status last verified
May 2017
First submitted
5 Sep 2014
Last updated
5 May 2017
Results posted
No
Data monitoring committee
No

Publications

  • Pfeifer ND, Goss SL, Swift B, Ghibellini G, Ivanovic M, Heizer WD, Gangarosa LM, Brouwer KL. Effect of Ritonavir on (99m)Technetium-Mebrofenin Disposition in Humans: A Semi-PBPK Modeling and In Vitro Approach to Predict Transporter-Mediated DDIs. CPT Pharmacometrics Syst Pharmacol. 2013 Jan 2;2(1):e20. doi: 10.1038/psp.2012.21.

    PubMed 23887590

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Technetium Tc 99M Mebrofenin in people with Non-alcoholic Steatohepatitis, 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 4 inclusion and 32 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 5 May 2017. 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?

Hepatic exposure (AUC0→∞) (time frame: 0-180 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02235233, which also lists 1 linked publication.

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 5 May 2017.

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