Nonalcoholic SteatohepatitisPhase 1STOPNASHNCT04152473
Safety and Tolerability of Oral Proglumide for NASH
A Phase 1 study testing Proglumide in people with Nonalcoholic Steatohepatitis, run by Georgetown University at 2 sites in United States.
Trial summary
This study is an open labelled Phase I/II clinical trial, designed to evaluate the safety and efficacy of an oral cholecystokinin (CCK) receptor antagonist, proglumide, at escalating doses in subjects with NASH. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis
- What is being tested?
- Proglumide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Dec 2019to 9 Sep 2022
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects ages 18 years to 85
- with radiographic imaging (by ultrasound, MRI, or CT) of fatty liver disease
- AND elevation in serum transaminases (ALT or AST).
- AND one of the following: BMI>30, hyperlipidemia, or evidence of poorly controlled diabetes such as HgbA1C >7
- Subjects on statins and with diabetes are eligible. Statins will be continued at the same dose for the duration of the study.
- Evidence of mild to moderate fibrosis on Fibroscan of F1 to F3 (kPa score < 14).
Who cannot join
- Evidence of active alcohol use/abuse.
- Chronic viral hepatitis B or hepatitis C, autoimmune hepatitis, drug induced liver disease.
- Those with evidence of cirrhosis on exam, histologically, or imaging, and a history of liver cancer are excluded.
- Laboratory tests that warrant exclusion include: Leukocyte Count <3.5 K/UL; Hemoglobin <9.5 g/dL; Blood Urea Nitrogen >30 mg/dL (hydrated); Creatinine >2.0 mg/dL, alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 5X ULN (upper limit normal), alkaline phosphatase (ALP)>2X ULN.
- Evidence of abnormal synthetic liver function including abnormal total bilirubin, platelet count <150,000 / mm3; and abnormal prothrombin time or increased INR (international normalized ratio) (unless on warfarin)
- History of gall bladder disease with gall bladder not surgically removed
Show all 12Show fewer
- Estimated glomerular filtration rate (eGFR of < 90 mL/min/1.73m2
- Type 1 diabetes mellitus
- Poorly controlled diabetes, defined by hemoglobin A1C (HbA1C) > 8, or diabetic patients that have not been on stable doses of anti-diabetic medication for at least 90 days prior to screening
- Pregnant or breast feeding
- A known preexisting medical or psychiatric condition that could interfere with the patient's ability to provide informed consent or participate in study conduct, or that may confound the study findings.
- Those found to have fibrosis score on Fibroscan of F0 or F4.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Georgetown University
Washington D.C., District of Columbia, 20007
Washington DC Veterans Affairs Medical Center
Washington D.C., District of Columbia, 20422
About this study
Official title: Phase 1 Study to Test Safety and Dose of Proglumide as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis (NASH)
This study is an open labelled Phase I/II clinical trial, designed to evaluate the safety and efficacy of an oral cholecystokinin (CCK) receptor antagonist, proglumide, at escalating doses in subjects with NASH.
An extended use protocol has been approved for subjects completing this study that show benefit or are at risk of Liver disease progression to continue on Proglumide at 1200 mg / day for an additional 3-9 months. Subjects in the extended protocol will have telephone visits monthly and in the research unit every 3 months for safety lab tests and research blood for fibrosis analysis.
Read the detailed description
This is a Phase 1single ascending dose study in 18 patients with ultrasound evidence of fatty liver disease AND increased hepatic transaminases. Proglumide will be using the single ascending dose study design in a Phase 1 fashion to determine the recommended Phase 2 dose (RP2D). Dose levels of proglumide will be: 400mg BID (twice daily); 400 mg TID (three times daily); 800 mg BID (twice daily).
Six patients will be enrolled in each cohort starting with the lowest dose of 400mg po BID (Twice daily)for 12 weeks.
Patients will be monitored for safety and toxicity by laboratory blood testing, physical examinations. Blood level for proglumide will be done at before proglumide at screening or baseline, week 2 and then week 4 and week 12.
Safety and toxicity will be monitored using the Common Terminology Criteria for Adverse Events v 5 and 'efficacy 'of the treatment will be evaluated by assessment of liver enzymes and fibroscan. The Phase 1 study design, we will follow the dose escalation scheme, where the dose increases after 6 subjects if a drug limiting toxicity (DLT) does not occur.
- Conditions
- Nonalcoholic Steatohepatitis
- Being tested
- Proglumide
- Keywords
- NASH
- 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.
ProglumideDrug
Also called Milid
oral CCK receptor antagonist
| Study group | Role | What they receive |
|---|---|---|
| Proglumide | Experimental | Open labelled proglumide treated Receives: Drug: Proglumide |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and toxicity
Number of participants with drug related Toxicity will follow standard Common Terminology Criteria for Adverse Events v.5,(CTCAE) criteria protocols. Toxicity is graded according to severity for symptoms obtained on the visit review of symptoms and according to blood tests collected at each scheduled visit
Measured: 12-weeks per dose
Recommended Phase 2 dose
Of the 3 doses to be tested which one has the fewest Drug related toxicity
Measured: for each dose, the number of AEs described over the 12 week period
Secondary outcomes (1)
Liver transaminases
A decrease in the serum aminotransferases (ALT and AST) in IU by 10% or more
Measured: Comparison of baseline serum ALT and AST values to week 12 week values in IU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2019
- Study start13 Dec 2019
- Primary completion31 Aug 2022
- Study completion9 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- open labelled sequential Phase I ascending dose study
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jill P Smith, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04152473
- Sponsor's protocol ID
- 0562
- Other IDs
- GU-3160
- Acronym
- STOPNASH
- Status last verified
- Oct 2022
- First submitted
- 20 Oct 2019
- Last updated
- 13 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data will be uploaded on the clinical trials website at the conclusion of the study and after accepted for publication
Publications
Tucker RD, Ciofoaia V, Nadella S, Gay MD, Cao H, Huber M, Safronenka A, Shivapurkar N, Kallakury B, Kruger AJ, Kroemer AHK, Smith JP. A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma. Dig Dis Sci. 2020 Jan;65(1):189-203. doi: 10.1007/s10620-019-05722-3. Epub 2019 Jul 11.
PubMed 31297627Rabiee A, Gay MD, Shivapurkar N, Cao H, Nadella S, Smith CI, Lewis JH, Bansal S, Cheema A, Kwagyan J, Smith JP. Safety and Dosing Study of a Cholecystokinin Receptor Antagonist in Non-alcoholic Steatohepatitis. Clin Pharmacol Ther. 2022 Dec;112(6):1271-1279. doi: 10.1002/cpt.2745. Epub 2022 Sep 27.
PubMed 36087237
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study to Test Safety and Dose of Proglumide as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT04152473
- Acronym / sponsor ID
- STOPNASH / 0562
- Conditions
- Nonalcoholic Steatohepatitis
- Keywords
- NASH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Study start
- 13 Dec 2019 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 9 Sep 2022 (actual)
- First posted
- 5 Nov 2019 (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.
This study is an open labelled Phase I/II clinical trial, designed to evaluate the safety and efficacy of an oral cholecystokinin (CCK) receptor antagonist, proglumide, at escalating doses in subjects with NASH.
An extended use protocol has been approved for subjects completing this study that show benefit or are at risk of Liver disease progression to continue on Proglumide at 1200 mg / day for an additional 3-9 months. Subjects in the extended protocol will have telephone visits monthly and in the research unit every 3 months for safety lab tests and research blood for fibrosis analysis.
Detailed description
This is a Phase 1single ascending dose study in 18 patients with ultrasound evidence of fatty liver disease AND increased hepatic transaminases. Proglumide will be using the single ascending dose study design in a Phase 1 fashion to determine the recommended Phase 2 dose (RP2D). Dose levels of proglumide will be: 400mg BID (twice daily); 400 mg TID (three times daily); 800 mg BID (twice daily).
Six patients will be enrolled in each cohort starting with the lowest dose of 400mg po BID (Twice daily)for 12 weeks.
Patients will be monitored for safety and toxicity by laboratory blood testing, physical examinations. Blood level for proglumide will be done at before proglumide at screening or baseline, week 2 and then week 4 and week 12.
Safety and toxicity will be monitored using the Common Terminology Criteria for Adverse Events v 5 and 'efficacy 'of the treatment will be evaluated by assessment of liver enzymes and fibroscan. The Phase 1 study design, we will follow the dose escalation scheme, where the dose increases after 6 subjects if a drug limiting toxicity (DLT) does not occur.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open labelled sequential Phase I ascending dose study
| Arm | Type | Receives |
|---|---|---|
| Proglumide | Experimental | Drug: ProglumideOpen labelled proglumide treated |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female subjects ages 18 years to 85
- with radiographic imaging (by ultrasound, MRI, or CT) of fatty liver disease
- AND elevation in serum transaminases (ALT or AST).
- AND one of the following: BMI>30, hyperlipidemia, or evidence of poorly controlled diabetes such as HgbA1C >7
- Subjects on statins and with diabetes are eligible. Statins will be continued at the same dose for the duration of the study.
Key exclusion criteria (12 listed)
- Evidence of active alcohol use/abuse.
- Chronic viral hepatitis B or hepatitis C, autoimmune hepatitis, drug induced liver disease.
- Those with evidence of cirrhosis on exam, histologically, or imaging, and a history of liver cancer are excluded.
- Laboratory tests that warrant exclusion include: Leukocyte Count <3.5 K/UL; Hemoglobin <9.5 g/dL; Blood Urea Nitrogen >30 mg/dL (hydrated); Creatinine >2.0 mg/dL, alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 5X ULN (upper limit normal), alkaline phosphatase (ALP)>2X ULN.
- Evidence of abnormal synthetic liver function including abnormal total bilirubin, platelet count <150,000 / mm3; and abnormal prothrombin time or increased INR (international normalized ratio) (unless on warfarin)
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 |
|---|---|---|
| ProglumideAlso: Milidoral CCK receptor antagonist | Drug | Proglumide |
Primary outcome
safety and toxicity
Time frame: 12-weeks per dose
Number of participants with drug related Toxicity will follow standard Common Terminology Criteria for Adverse Events v.5,(CTCAE) criteria protocols. Toxicity is graded according to severity for symptoms obtained on the visit review of symptoms and according to blood tests collected at each scheduled visit
Recommended Phase 2 dose
Time frame: for each dose, the number of AEs described over the 12 week period
Of the 3 doses to be tested which one has the fewest Drug related toxicity
1 secondary outcome
Liver transaminases
Time frame: Comparison of baseline serum ALT and AST values to week 12 week values in IU
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 13 Oct 2022.
- Background: PubMed 31297627Tucker RD, Ciofoaia V, Nadella S, Gay MD, Cao H, Huber M, Safronenka A, Shivapurkar N, Kallakury B, Kruger AJ, Kroemer AHK, Smith JP. A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma. Dig Dis Sci. 2020 Jan;65(1):189-203. doi: 10.1007/s10620-019-05722-3. Epub 2019 Jul 11.
- Background: PubMed 36087237Rabiee A, Gay MD, Shivapurkar N, Cao H, Nadella S, Smith CI, Lewis JH, Bansal S, Cheema A, Kwagyan J, Smith JP. Safety and Dosing Study of a Cholecystokinin Receptor Antagonist in Non-alcoholic Steatohepatitis. Clin Pharmacol Ther. 2022 Dec;112(6):1271-1279. doi: 10.1002/cpt.2745. Epub 2022 Sep 27.
- Individual participant dataSharing planned: Yes. The data will be uploaded on the clinical trials website at the conclusion of the study and after accepted for publication
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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.
Jill P Smith, MD principal investigator
Georgetown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Proglumide in people with Nonalcoholic Steatohepatitis, run by Georgetown University at 2 sites 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 6 inclusion and 12 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 13 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
safety and toxicity (time frame: 12-weeks per dose). The study lists 2 primary outcomes in all. 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 NCT04152473, which also lists 2 linked publications.
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 13 Oct 2022.