Non-alcoholic SteatohepatitisPhase 2HEFITEPNCT06160271
Study of Liver Fibrosis Stage Assessment by Fibroblast Activation Protein Imaging in Patients With Biopsy for Suspected or Proven Nonalcoholic Steatohepatitis
A Phase 2 study testing PET scan of 68Ga-FAPI in people with Non-alcoholic Steatohepatitis, run by Central Hospital, Nancy, France.
Trial summary
Non-alcoholic fatty liver disease (NAFLD), estimated to be 17% prevalent in France, can lead to non-alcoholic steatohepatitis (NASH), which in turn can progress to fibrosis, the ultimate stage of which is cirrhosis, a major cause of liver transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-alcoholic Steatohepatitis
- What is being tested?
- PET scan of 68Ga-FAPI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2024to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals with recent liver biopsy for suspected or confirmed NASH
- Individuals of legal age, who have received full information on the organization of the research and have signed an informed consent form.
- Person, affiliated to a social security scheme or beneficiary of such a scheme.
- Person who has undergone a preliminary clinical examination appropriate to the research.
- Histological stage of fibrosis obtained at biopsy in accordance with the planned numbers (an equivalent number of patients with histological stages >2 and ≤ 2 must be recruited in each center, and a number of at least 16 patients must be included by all centers in each of the 4 groups of histological stages of fibrosis).
Who cannot join
- Known hypersensitivity to 68Ga-FAPI-46 or to any of the excipients or components of the radiopharmaceutical.
- Infection with HCV/HBV.
- Decompensated cirrhosis (ascites, hepatic insufficiency, hepatorenal syndrome, etc.).
- Known hepatocellular carcinoma.
- Steatogenic treatment (corticosteroid, Tamoxifen, Amiodarone, Methotrexate).
- Excessive alcohol consumption in the last 5 years (>210 g/week in men, >140 g/week in women).
- Clinically unstable state not suitable for 68Ga-FAPI-46 PET/CT scan.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Pilot Study of Liver Fibrosis Stage Assessment by Tep Fibroblast Activation Protein Imaging (68Ga-FAPI-46 TEP/TDM) in Patients With Biopsy for Suspected or Proven Nonalcoholic Steatohepatitis (NASH)
Non-alcoholic fatty liver disease (NAFLD), estimated to be 17% prevalent in France, can lead to non-alcoholic steatohepatitis (NASH), which in turn can progress to fibrosis, the ultimate stage of which is cirrhosis, a major cause of liver transplantation. The prevalence of NASH is increasing worldwide, along with that of type 2 diabetes and obesity. Significant liver fibrosis is estimated to affect at least 2.6% of the adult population in France.
The prognosis of patients with NASH is directly linked to the stage of liver fibrosis determined by biopsy, and these biopsies must now be repeated to assess the effect of treatments. Hepatic fibrosis is traditionally classified into five stages, from the absence of fibrosis (F0) to severe cirrhosis (F4), and passage from one stage to another is considered to demonstrate significant variation, likely to impact prognosis.
Read more
However, liver biopsy is painful. It can only analyze a very small proportion of liver volume (1/50,000), whereas the distribution of fibrosis is generally heterogeneous. Above all, biopsy is not devoid of risks, primarily hemorrhage, which can sometimes be severe or even fatal.
In line with current recommendations, clinical-biological algorithms, as well as ultrasound elastography or MRI, are used to assess the risk of fibrosis and the value of a liver biopsy. Generally speaking, these tests have the advantage of very good negative predictive values, making it possible to exclude the possibility of significant fibrosis in a large proportion of patients. However, their positive predictive values are weaker, even when these tests are combined. Above all, they do not allow us to follow the evolution of the fibrosis stage over time. This is why liver biopsies remain indispensable for determining the stage and severity of hepatic fibrosis and monitoring its evolution. It is therefore essential to develop more precise, non-invasive methods for accurately assessing the extent of liver fibrosis. This is the objective of the FreSH national cohort, which uses conventional biological techniques and in which our patients will also be included.
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD), estimated to be 17% prevalent in France, can lead to non-alcoholic steatohepatitis (NASH), which in turn can progress to fibrosis, the ultimate stage of which is cirrhosis, a major cause of liver transplantation. The prevalence of NASH is increasing worldwide, along with that of type 2 diabetes and obesity. Significant liver fibrosis is estimated to affect at least 2.6% of the adult population in France The prognosis of patients with NASH is directly linked to the stage of liver fibrosis determined by biopsy, and these biopsies must now be repeated to assess the effect of treatments. Hepatic fibrosis is traditionally classified into five stages, from the absence of fibrosis (F0) to severe cirrhosis (F4), and passage from one stage to another is considered to demonstrate significant variation, likely to impact prognosis.
However, liver biopsy is painful. It can only analyze a very small proportion of liver volume (1/50,000), whereas the distribution of fibrosis is generally heterogeneous. Above all, biopsy is not devoid of risks, primarily hemorrhage, which can sometimes be severe or even fatal.
In line with current recommendations, clinical-biological algorithms, as well as ultrasound elastography or MRI, are used to assess the risk of fibrosis and the value of a liver biopsy. Generally speaking, these tests have the advantage of very good negative predictive values, making it possible to exclude the possibility of significant fibrosis in a large proportion of patients. However, their positive predictive values are weaker, even when these tests are combined. Above all, they do not allow us to follow the evolution of the fibrosis stage over time. This is why liver biopsies remain indispensable for determining the stage and severity of hepatic fibrosis and monitoring its evolution. It is therefore essential to develop more precise, non-invasive methods for accurately assessing the extent of liver fibrosis. This is the objective of the FreSH national cohort, which uses conventional biological techniques and in which our patients will also be included.
The hypothesis behind this initial pilot study is that 68Ga-FAPI-46 PET/CT imaging, which targets fibroblast activating protein (FAP), could provide a precise assessment of the severity and stages of liver fibrosis, as well as its distribution throughout the liver volume, and could ultimately be a useful tool for non-invasive monitoring of patients undergoing treatment. This technique has already been validated for the detection of numerous cancers, including hepatocarcinomas, and is capable of assessing renal fibrosis (pilot study with 15 patients), with a good correlation to biopsy and a direct link to glomerular filtration rate.
Targeted receptor (FAP) data also strongly support our hypothesis:
- FAP expression is negligible in healthy livers and proportional to the degree of fibrosis in pathological livers.
- Low plasma FAP concentrations rule out the hypothesis of hepatic fibrosis. PAF inhibitors also represent a very promising avenue of therapeutic research in NASH.
The HEFITEP study will assess for the first time the discriminative power of 68Ga-FAPI-46 PET/CT for grading liver fibrosis with reference to centrally analyzed liver biopsy in patients biopsied for suspected or proven non-alcoholic steatohepatitis (NASH).
- Conditions
- Non-alcoholic Steatohepatitis
- Being tested
- PET scan of 68Ga-FAPI
- 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.
PET scan of 68Ga-FAPIDrug
Use of a positron emission tomograph equipped with an X-ray scanner (PET/CT), essential for recording images after injection of a positron-emitting radiopharmaceutical (in this study, 68Ga-FAPI-46).
| Study group | Role | What they receive |
|---|---|---|
| TEP 68Ga-FAPI | Experimental | Use of a positron emission tomograph equipped with an X-ray scanner (PET/CT), essential for recording images after injection of a positron-emitting radiopharmaceutical (in this study, 68Ga-FAPI-46). Receives: Drug: PET scan of 68Ga-FAPI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Capture intensity measurement
Measurement of 68Ga-FAPI-46 uptake intensity, with standardized uptake values in areas centred on the biopsy sites, the reference then being a classification of fibrosis stages determined by centralized biopsy rereading
Measured: 1 year
Secondary outcomes (5)
Standardized Uptake Value threshold values associated with each of the four fibrosis histological stage groups
Standardized Uptake Value threshold values associated with each of the four fibrosis histological stage groups (stages 4, 3, 2 and < 2) by the naive Bayes classifier.
Measured: 1 year
Localization of the capture zone with maximum activity
Localization of the capture zone with maximum activity (SUVmax and SUV pic zones, respectively)
Measured: 1 year
Search, on whole-body images, for 68Ga-FAPI-46 uptake
Search, on whole-body images, for 68Ga-FAPI-46 uptake foci located outside the tracer's normal elimination zones (urinary excretory tracts), and which may correspond to abnormal areas of fibrosis and/or inflammation, or even cancer
Measured: 1 year
Intra-class correlation coefficients
Intra-class correlation coefficients and their 95% confidence intervals.
Measured: 1 year
Variation in the degree of prediction of the four groups of histological stages of fibrosis
Variation in the degree of prediction of the four groups of histological stages of fibrosis when variables from 68Ga-FAPI-46 PET/CT are added to variables from usual clinical-biological scores
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start1 Sep 2024 (estimated)
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe 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 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elodie CHEVALIER, Central Hospital, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06160271
- Sponsor's protocol ID
- 2022PI044
- Acronym
- HEFITEP
- Status last verified
- Nov 2023
- First submitted
- 29 Nov 2023
- Last updated
- 9 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Liver Fibrosis Stage Assessment by Tep Fibroblast Activation Protein Imaging (68Ga-FAPI-46 TEP/TDM) in Patients With Biopsy for Suspected or Proven Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT06160271
- Acronym / sponsor ID
- HEFITEP / 2022PI044
- Conditions
- Non-alcoholic Steatohepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 7 Dec 2023 (actual)
- 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.
Non-alcoholic fatty liver disease (NAFLD), estimated to be 17% prevalent in France, can lead to non-alcoholic steatohepatitis (NASH), which in turn can progress to fibrosis, the ultimate stage of which is cirrhosis, a major cause of liver transplantation. The prevalence of NASH is increasing worldwide, along with that of type 2 diabetes and obesity. Significant liver fibrosis is estimated to affect at least 2.6% of the adult population in France.
The prognosis of patients with NASH is directly linked to the stage of liver fibrosis determined by biopsy, and these biopsies must now be repeated to assess the effect of treatments. Hepatic fibrosis is traditionally classified into five stages, from the absence of fibrosis (F0) to severe cirrhosis (F4), and passage from one stage to another is considered to demonstrate significant variation, likely to impact prognosis.
However, liver biopsy is painful. It can only analyze a very small proportion of liver volume (1/50,000), whereas the distribution of fibrosis is generally heterogeneous. Above all, biopsy is not devoid of risks, primarily hemorrhage, which can sometimes be severe or even fatal.
In line with current recommendations, clinical-biological algorithms, as well as ultrasound elastography or MRI, are used to assess the risk of fibrosis and the value of a liver biopsy. Generally speaking, these tests have the advantage of very good negative predictive values, making it possible to exclude the possibility of significant fibrosis in a large proportion of patients. However, their positive predictive values are weaker, even when these tests are combined. Above all, they do not allow us to follow the evolution of the fibrosis stage over time. This is why liver biopsies remain indispensable for determining the stage and severity of hepatic fibrosis and monitoring its evolution. It is therefore essential to develop more precise, non-invasive methods for accurately assessing the extent of liver fibrosis. This is the objective of the FreSH national cohort, which uses conventional biological techniques and in which our patients will also be included.
Detailed description
Non-alcoholic fatty liver disease (NAFLD), estimated to be 17% prevalent in France, can lead to non-alcoholic steatohepatitis (NASH), which in turn can progress to fibrosis, the ultimate stage of which is cirrhosis, a major cause of liver transplantation. The prevalence of NASH is increasing worldwide, along with that of type 2 diabetes and obesity. Significant liver fibrosis is estimated to affect at least 2.6% of the adult population in France The prognosis of patients with NASH is directly linked to the stage of liver fibrosis determined by biopsy, and these biopsies must now be repeated to assess the effect of treatments. Hepatic fibrosis is traditionally classified into five stages, from the absence of fibrosis (F0) to severe cirrhosis (F4), and passage from one stage to another is considered to demonstrate significant variation, likely to impact prognosis.
However, liver biopsy is painful. It can only analyze a very small proportion of liver volume (1/50,000), whereas the distribution of fibrosis is generally heterogeneous. Above all, biopsy is not devoid of risks, primarily hemorrhage, which can sometimes be severe or even fatal.
In line with current recommendations, clinical-biological algorithms, as well as ultrasound elastography or MRI, are used to assess the risk of fibrosis and the value of a liver biopsy. Generally speaking, these tests have the advantage of very good negative predictive values, making it possible to exclude the possibility of significant fibrosis in a large proportion of patients. However, their positive predictive values are weaker, even when these tests are combined. Above all, they do not allow us to follow the evolution of the fibrosis stage over time. This is why liver biopsies remain indispensable for determining the stage and severity of hepatic fibrosis and monitoring its evolution. It is therefore essential to develop more precise, non-invasive methods for accurately assessing the extent of liver fibrosis. This is the objective of the FreSH national cohort, which uses conventional biological techniques and in which our patients will also be included.
The hypothesis behind this initial pilot study is that 68Ga-FAPI-46 PET/CT imaging, which targets fibroblast activating protein (FAP), could provide a precise assessment of the severity and stages of liver fibrosis, as well as its distribution throughout the liver volume, and could ultimately be a useful tool for non-invasive monitoring of patients undergoing treatment. This technique has already been validated for the detection of numerous cancers, including hepatocarcinomas, and is capable of assessing renal fibrosis (pilot study with 15 patients), with a good correlation to biopsy and a direct link to glomerular filtration rate.
Targeted receptor (FAP) data also strongly support our hypothesis:
- FAP expression is negligible in healthy livers and proportional to the degree of fibrosis in pathological livers.
- Low plasma FAP concentrations rule out the hypothesis of hepatic fibrosis. PAF inhibitors also represent a very promising avenue of therapeutic research in NASH.
The HEFITEP study will assess for the first time the discriminative power of 68Ga-FAPI-46 PET/CT for grading liver fibrosis with reference to centrally analyzed liver biopsy in patients biopsied for suspected or proven non-alcoholic steatohepatitis (NASH).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TEP 68Ga-FAPI | Experimental | Drug: PET scan of 68Ga-FAPIUse of a positron emission tomograph equipped with an X-ray scanner (PET/CT), essential for recording images after injection of a positron-emitting radiopharmaceutical (in this study, 68Ga-FAPI-46). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Individuals with recent liver biopsy for suspected or confirmed NASH
- Individuals of legal age, who have received full information on the organization of the research and have signed an informed consent form.
- Person, affiliated to a social security scheme or beneficiary of such a scheme.
- Person who has undergone a preliminary clinical examination appropriate to the research.
- Histological stage of fibrosis obtained at biopsy in accordance with the planned numbers (an equivalent number of patients with histological stages >2 and ≤ 2 must be recruited in each center, and a number of at least 16 patients must be included by all centers in each of the 4 groups of histological stages of fibrosis).
Key exclusion criteria (7 listed)
- Known hypersensitivity to 68Ga-FAPI-46 or to any of the excipients or components of the radiopharmaceutical.
- Infection with HCV/HBV.
- Decompensated cirrhosis (ascites, hepatic insufficiency, hepatorenal syndrome, etc.).
- Known hepatocellular carcinoma.
- Steatogenic treatment (corticosteroid, Tamoxifen, Amiodarone, Methotrexate).
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 |
|---|---|---|
| PET scan of 68Ga-FAPIUse of a positron emission tomograph equipped with an X-ray scanner (PET/CT), essential for recording images after injection of a positron-emitting radiopharmaceutical (in this study, 68Ga-FAPI-46). | Drug | TEP 68Ga-FAPI |
Primary outcome
Capture intensity measurement
Time frame: 1 year
Measurement of 68Ga-FAPI-46 uptake intensity, with standardized uptake values in areas centred on the biopsy sites, the reference then being a classification of fibrosis stages determined by centralized biopsy rereading
5 secondary outcomes
Standardized Uptake Value threshold values associated with each of the four fibrosis histological stage groups
Time frame: 1 year
Localization of the capture zone with maximum activity
Time frame: 1 year
Search, on whole-body images, for 68Ga-FAPI-46 uptake
Time frame: 1 year
Intra-class correlation coefficients
Time frame: 1 year
Variation in the degree of prediction of the four groups of histological stages of fibrosis
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2024.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PET scan of 68Ga-FAPI in people with Non-alcoholic Steatohepatitis, run by Central Hospital, Nancy, France.
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 5 inclusion and 7 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: opening soon, as of the sponsor's last update on 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chevalier Elodie, MD (+3383153475, e.chevalier@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Capture intensity measurement (time frame: 1 year). 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 9 Feb 2024.