Clinical trial NCT04449536: Cysteine-lowering Treatment With Mesna
Official title: Cysteine-lowering Treatment With Mesna Against Obesity: Phase I Dose-finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Drug Effect
Keywords: Cysteine
Phase 1
Mesna
Lead sponsor: University of Oslo
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
name: University of Oxford
First posted: 2020-06-29
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.
timeFrame: Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3
Secondary outcomes:
measure: Pharmacokinetic parameter - maximum plasma concentration (Cmax)
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Pharmacokinetic parameter - area under the plasma concentration-time curve (AUC)
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Pharmacokinetic parameter - elimination rate constant (Kel)
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Pharmacokinetic parameter - dose linearity
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Change in plasma cystine, free reduced cysteine, and protein bound cysteine
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Urine excretion of cysteine
timeFrame: During the first 24 hours after Mesna administration
measure: Safety of Mesna
timeFrame: During the first 5 days after Mesna administration
Other outcomes:
measure: Changes in plasma and urine sulfur amino acids and related metabolites
timeFrame: Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Changes in plasma biomarker concentration - glucose
timeFrame: During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Changes in plasma biomarker concentration - insulin
timeFrame: During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
measure: Changes in plasma biomarker concentration - lipids
timeFrame: During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
Locations:
city: Oslo
country: Norway
facility: University of Oslo
Study officials:
affiliation: University of Oslo
name: Kjetil Retterstøl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: