Cysteine-lowering Treatment With Mesna

Obesity Clinical Trial

— CYLOB  

Official title:

Cysteine-lowering Treatment With Mesna Against Obesity: Phase I Dose-finding Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04449536
• Other study ID #: EudraCT: 2019-003412-32
• Status: Completed
• Phase: Phase 1
• Start date: November 2, 2020
• Est. completion date: October 21, 2021

Study information

• Verified date: May 2022
• Source: University of Oslo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the efficacy of the drug Mesna® (Uromitexan) in healthy participants with overweight or obesity with respect to change in plasma concentrations of total cysteine, following single ascending doses of oral Mesna.

Description:

In both animal experiments and human studies, cysteine in the blood is strongly associated with obesity. In rodents, changes in cysteine induced by dietary means are accompanied by changes in fat mass.

In this phase I, single ascending dose study the investigators will determine the effects of Mesna in healthy volunteers with overweight and obesity with focus on its effects on plasma total cysteine concentrations. The aim of this dose-finding clinical trial is to determine the lowest single oral Mesna dose that will lower plasma total cysteine concentrations by 30% using pharmacokinetic (PK)/ pharmacodynamic (PD) modelling. The investigators will further evaluate the effect of Mesna on plasma cysteine fractions and related metabolites, urinary cysteine excretion, safety and adverse drug reactions, and plasma biomarkers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: October 21, 2021
• Est. primary completion date: October 21, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• BMI between BMI 27-40 kg/m2

• Age between 18-55 years

• Male

• Healthy as determined by medical evaluation, medical history, physical examination, 12-lead ECG, and laboratory tests

Exclusion Criteria:

• Presence of chronic disease

• Chronic drug use

• Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing

• Veganism

• Strenuous physical activity =3 times every week

• Smoking

Related Conditions & MeSH terms

• Drug Effect
• Obesity

Intervention

Drug:
• Mesna
Administration of a single oral dose, using film-coated tablets of either 400 mg or 600 mg or a combination of maximum 3 tablets up to a maximum of 1600 mg

Locations

Country	Name	City	State
Norway	University of Oslo	Oslo

Sponsors (3)

Lead Sponsor	Collaborator
University of Oslo	Oslo University Hospital, University of Oxford

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in plasma and urine sulfur amino acids and related metabolites	Estimated AUCs	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Other	Changes in plasma biomarker concentration - glucose	Estimated AUC	During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
Other	Changes in plasma biomarker concentration - insulin	Estimated AUC	During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
Other	Changes in plasma biomarker concentration - lipids	Estimated AUC	During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
Primary	Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.	Nadir plasma total cysteine concentrations	Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3
Secondary	Pharmacokinetic parameter - maximum plasma concentration (Cmax)	Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Secondary	Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)	Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Secondary	Pharmacokinetic parameter - area under the plasma concentration-time curve (AUC)	Area under the plasma Mesna concentration-time curve (AUC)0-inf after a single oral Mesna dose	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Secondary	Pharmacokinetic parameter - elimination rate constant (Kel)	Elimination rate constant (Kel) for Mesna after a single oral Mesna dose	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Secondary	Pharmacokinetic parameter - dose linearity	Dose linearity of Mesna after a single oral Mesna dose	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Secondary	Change in plasma cystine, free reduced cysteine, and protein bound cysteine	Estimated AUCs	Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Secondary	Urine excretion of cysteine	Cumulative and fractional excretion of total cysteine and Mesna	During the first 24 hours after Mesna administration
Secondary	Safety of Mesna	Occurrence/prevalence of side effects, adverse events, and serious adverse events	During the first 5 days after Mesna administration