Effect of treatment with Semaglutide on cognitive function, brain inflammation and nitrogen-conversion in the liver in patients with non-alcoholic steatohepatitis: A randomized placebo-controlled trial

Phase 1

• Conditions: on-alcoholic steatohepatitis; MedDRA version: 22.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2020-004373-50-DK
• Lead Sponsor: Aarhus University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-15
• Last Update Posted: 26 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Age 18 - 69 years.
2. Biopsy-proven NASH
3. Understands and speaks Danish
4. Alcohol consumption < 40g/day
5. Exclusion of other liver pathology
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

1. Known chronic inflammatory disease
2. Contraindication for liver biopsy: Anamnestic, clinical or laboratory signs of hemorrhagic diatesis, infection at the insertion area or focal changes in the liver
3. Diabetes Mellitus type 1 or 2 (HbA1c > 48 mmol/mol)
4. Bacterial infection
5. Known cancer
6. Known neurolodegenerative disease
7. Known severe impairment of hearing or eye sight
8. Known allergy towards one or more ingredients in the Ozempic® formula
9. Treatment with antipsychotics or other psychotropic drugs with sedative effects
10. Treatment with corticosteroids within the past 8 weeks
11. Breastfeeding
12. Pregnancy demonstrated by a positive pregnancy test or desire to become pregnant and no use of safe anti-conception (p-pills, intrauterine device, sterilised)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effect of treatment with Semaglutide on cognitive function in patients with non-alcoholic steatohepatitis.;Secondary Objective: To investigate how treatment with Semaglutide affects known factors involved in cognitive problems in patients with liver disease, here brain inflammation and impaired nitrogen conversion in the liver.;Primary end point(s): Change in cognitive function assessed by the Portosystemic Encephalopathy (PSE) test – measured as Portosystemic Hepatic Encephalopathy Score (PHES).;Timepoint(s) of evaluation of this end point: 6 months (28 weeks).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Change in attention and psychomotor speed assessed by continuous reaction time (CRT) – measured as Index score.<br>•Change in function of separate cognitive domains assessed by a neuropsychological test battery – measured as test scores in individual neuropsychological tests.<br>•Change in neuroinflammation assessed by PET/MRI of the brain – measured as 11C-PK11195 binding potential in brain regions.<br>•Change in systemic inflammation assessed by levels of proinflammatory cytokines in blood.<br>•Change in hepatic urea synthesis function assessed by the Functional Hepatic Nitrogen Clearance (FHNC) method – measured as FHNC.<br>•Change in NASH severity assessed by histological examination of tissue from liver biopsy – measured as NAS-score and Kleiner fibrosis grade.;Timepoint(s) of evaluation of this end point: 1 month (4 weeks) and 6 months (28 weeks).