Back to results

Safety and Tolerability of Oral Proglumide for NASH (STOPNASH)

Primary Purpose

Nonalcoholic Steatohepatitis

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Proglumide

About this trial

This is an interventional other trial for Nonalcoholic Steatohepatitis focused on measuring NASH

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).

Exclusion Criteria:

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
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.

Sites / Locations

Georgetown University
Washington DC Veterans Affairs Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Proglumide

Arm Description

Open labelled proglumide treated

Outcomes

Primary Outcome Measures

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

Recommended Phase 2 dose

Of the 3 doses to be tested which one has the fewest Drug related toxicity

Secondary Outcome Measures

Liver transaminases

A decrease in the serum aminotransferases (ALT and AST) in IU by 10% or more

Full Information

NCT ID

NCT04152473

First Posted

October 20, 2019

Last Updated

October 10, 2022

Sponsor

Georgetown University

1. Study Identification

Unique Protocol Identification Number

NCT04152473

Brief Title

Safety and Tolerability of Oral Proglumide for NASH

Acronym

STOPNASH

Official Title

Phase 1 Study to Test Safety and Dose of Proglumide as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis (NASH)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

December 13, 2019 (Actual)

Primary Completion Date

August 31, 2022 (Actual)

Study Completion Date

September 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Georgetown University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nonalcoholic Steatohepatitis

Keywords

NASH

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

open labelled sequential Phase I ascending dose study

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Proglumide

Arm Type

Experimental

Arm Description

Open labelled proglumide treated

Intervention Type

Drug

Intervention Name(s)

Proglumide

Other Intervention Name(s)

Milid

Intervention Description

oral CCK receptor antagonist

Primary Outcome Measure Information:

Title

safety and toxicity

Description

Time Frame

12-weeks per dose

Title

Recommended Phase 2 dose

Description

Of the 3 doses to be tested which one has the fewest Drug related toxicity

Time Frame

for each dose, the number of AEs described over the 12 week period

Secondary Outcome Measure Information:

Title

Liver transaminases

Description

A decrease in the serum aminotransferases (ALT and AST) in IU by 10% or more

Time Frame

Comparison of baseline serum ALT and AST values to week 12 week values in IU

Other Pre-specified Outcome Measures:

Title

NASH score by Fibroscan

Description

liver stiffness kPa score with a decrease by 4kPa and steatosis (CAPS) score in dB/m. a decline of 30 dB/m

Time Frame

baseline compared to week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). Exclusion Criteria: 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jill P Smith, MD

Organizational Affiliation

Georgetown University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Georgetown University

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

Washington DC Veterans Affairs Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20422

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The data will be uploaded on the clinical trials website at the conclusion of the study and after accepted for publication

IPD Sharing Time Frame

After the publication at the completion of the study

IPD Sharing Access Criteria

Available on clinicaltrials.gov website for 1 year after publication

Citations:

PubMed Identifier

31297627

Citation

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.

Results Reference

background

PubMed Identifier

36087237

Citation

Rabiee 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.

Results Reference

background

Learn more about this trial

Safety and Tolerability of Oral Proglumide for NASH

We'll reach out to this number within 24 hrs