Effect of orlistat on LIVER fat content in obese subjects with NAFLD and High concEntrAtion of pLasma proneurotensin THrough inhibition of neurotensin secretion and action

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

9 Jan 2024 → 2 Jun 2025

Decision date (initial)

2023-01-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Research Council (Advanced grant) 885003-PREVENT-2024

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces percentual Liver Fat Content (LFC%) in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well high plasma concentration of pro-NTS (>150 pmol/L).

Secondary objectives 8

1. To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces body weight, in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
2. To test if 24 weeks treatment with orlistat as compared with control therapy significantly improves insulin sensitivity (assessed by the “Homeostatic Model Assessment of insulin resistance”, “HOMA-IR”), in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
3. To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces fasting plasma glucose, in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
4. To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces plasma glucose 2-hours after an oral glucose load in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
5. To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces plasma triglycerides in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
6. To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces plasma LDL-cholesterol in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
7. To test if 24 weeks treatment with orlistat as compared with control therapy significantly reduces systolic blood pressure in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).
8. To test if 24 weeks treatment with orlistat as compared with control therapy significantly increases HDL-cholesterol in individuals with obesity (BMI≥30 kg/m2), presence of NAFLD as well as high plasma concentration of pro-NTS (>150 pmol/L).

Conditions and MedDRA coding

Non-Alcoholic Fatty Liver Disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. *Age 20-65 years
2. *Written informed consent
3. *Negative pregnancy test in women of child bearing potential (WOCBP)
4. *Body mass index ≥30kg/m2
5. *plasma concentration of pro-NTS>150 pmol/L
6. *LFC% >5.6% in the absence of other causes of steatosis than NAFLD

Exclusion criteria 20

1. *Allergy or hypersensitivity of orlistat
2. *Chronic malabsorption syndrome
3. *Breast feeding
4. *Planned or known ongoing pregnancy
5. *Cholestasis
6. *Liver disease other than NAFLD
7. *Diabetes Mellitus treated with insulin
8. *Inflammatory bowel disease
9. *Irritable bowel disease
10. *Hypothyroidism
11. *Hepatitis C
12. *Epilepsy
13. *Concomitant medication with any of the following: any oral anticoagulants, any anti-epileptic medications, ciclosporin, corticosteroids, diltiazem, amiodarone, antiviral HIV therapy, levothyroxine, and acarbose
14. *Estimated glomerular filtration rate <30 mL/min
15. *Claustrophobia
16. *Implants contraindicating magnetic resonance imaging such as pacemaker, metallic clips in blood vessels or brain and cochlea implant
17. *Alcohol intake >20g per day
18. *Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation
19. *Treatment or disease which, according to the investigator, can affect treatment or study results.
20. *Participation or recent participation in a clinical study with an investigational product (within 30 days). Previous participation in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is the treatment group difference in 6-month change (LFC% at week 24 – LFC% week -1) of absolute LFC%

Secondary endpoints 8

1. Between group (orlistat vs control) difference of 24-week change in body weight
2. Between group (orlistat vs control) difference of 24-week change in insulin sensitivity (assessed by the “Homeostatic Model Assessment of insulin resistance”, “HOMA-IR”)
3. Between group (orlistat vs control) difference of 24-week change in fasting plasma glucose.
4. Between group (orlistat vs control) difference of 24-week change in plasma glucose 2-hours after a 75 gram oral glucose load
5. Between group (orlistat vs control) difference of 24-week change in plasma triglycerides
6. Between group (orlistat vs control) difference of 24-week change in plasma LDL-cholesterol
7. Between group (orlistat vs control) difference of 24-week change in systolic blood pressure
8. Between group (orlistat vs control) difference of 24-week change in HDL-cholesterol

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Olle Melander

Public contact point

Organisation

Region Skane

Contact name

Olle Melander

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications