Role of Interleukin (IL)-1 in Postprandial Fatigue - The Chäschüechli 2 Study (Chäs2)

Role of IL-1 in Postprandial Fatigue - The Chäschüechli 2 Study

Role of IL-1 in postprandial fatigue - The Chäschüechli 2 Study It is a randomized, single dose, placebo-controlled, double blind, cross-over, proof-of-concept study.

16 healthy young men will be included in this study. The objective of this study is to evaluate if severity of postprandial fatigue is driven by IL-1.

Since fatigue is associated with increased cytokine levels, and since fatigue in chronic inflammatory settings, such as type 2 diabetes, can be reduced by inhibition of IL-1β, postprandial fatigue might also respond to anti-inflammatory intervention with IL-1 inhibition.

The aim of the study is to investigate whether postprandial fatigue is, at least in part, driven by the IL-1 system.

Study Overview

• Status: Completed
• Conditions: Adiposity
• Intervention / Treatment: Drug: Anakinra; Drug: NaCl

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, CH-4031 Basel
    • University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Male subjects

• non-smoking
• apparently healthy
• BMI >18 and ≤28 kg/m2 or BMI >30 and ≤35 kg/m2
• Age 20-65 years
• Subject is usually eating breakfast and lunch
• Willingness to use contraceptive measures adequate to prevent the subject's partner from becoming pregnant during the study. Adequate contraceptive measures include hormonal methods used for two or more cycles prior to screening (e.g., oral contraceptive pills, contraceptive patch, or contraceptive vaginal ring), double barrier methods (e.g., contraceptive sponge, diaphragm used in conjunction with contraceptive foam or jelly, and condom used in conjunction with contraceptive foam or jelly), intrauterine methods (IUD) and sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner).
• Owner of a smartphone so they will be able to download and use the sleeping APP, Sleep cycle, prior to the study days.

Exclusion Criteria:

Subjects will be excluded from the study if they meet any of the following criteria:

• Night shift workers
• Subjects suffering from sleep disturbances
• Clinical signs of infection in the week before inclusion or history of infection during the last 2 months (CRP >5mg/l)
• Impaired fasting glucose (fasting plasma glucose >5.5mmol/l)
• Hematologic disease (leukocyte count < 1.5x109/l, hemoglobin <11 g/dl, platelets <100 x 103/ul)
• Kidney disease (creatinine > 1.5 mg/dl))
• Liver disease (transaminases >2x upper normal range)
• Heart disease
• Pulmonary disease
• Inflammatory disease
• History of carcinoma
• History of tuberculosis
• Alcohol consumption >40g/d
• Smoking
• Known allergy towards Kineret
• Known allergy to ingredients of the test meal
• Current treatment with any drug in the week before inclusion, including vitamin supplementation (especially vitamin C and E)
• Use of any investigational drug within 30 days prior to enrolment or within 5 half-lives of the investigational drug, whichever is longer
• Subject refusing or unable to give written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal BMI; Healthy young men, normal BMI (BMI >18 and ≤28 kg/m2) will receive interventions Anakinra and sodium Chloride (NaCl)	Drug: Anakinra; Subjects will receive Anakinra infusion and afterwards they will be fed a very fat containing meal, and postprandial fatigue will be measured regularly until 3,5 hour after the meal.; Other Names: Kineret; Drug: NaCl; subjects will receive NaCl infusion and afterwards they will be fed a very fat containing meal, and postprandial fatigue will be measured regularly until 3,5 hour after the meal.; Other Names: sodium chloride
Experimental: Overweight; Healthy young men (BMI >30 and ≤35 kg/m2) will receive interventions Anakinra and NaCl	Drug: Anakinra; Subjects will receive Anakinra infusion and afterwards they will be fed a very fat containing meal, and postprandial fatigue will be measured regularly until 3,5 hour after the meal.; Other Names: Kineret; Drug: NaCl; subjects will receive NaCl infusion and afterwards they will be fed a very fat containing meal, and postprandial fatigue will be measured regularly until 3,5 hour after the meal.; Other Names: sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is change in fatigue measured by the SSS (Stanford Sleepiness Scale) between groups treated with Anakinra vs. placebo	Fatigue will be measured by using the SSS (Stanford Sleepiness Scale)	7 to 9 days (change between study day 1 and study day 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in postprandial glucose, insulin, C-peptide, glucagon-like Peptide (GLP)-1(active/total), GIP(active/total), PYY, IL-6, tumor necrosis factor (TNF)-alfa, sCRP and cortisol due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in heart rate due to any treatment (Anakinra vs. saline)	Pulse watch	7 to 9 days (change between study day 1 and study day 2)
Change in insulin due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in C-peptide due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in GLP-1(active/total) due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in GIP(active/total) due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in PYY due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in IL-6 due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in TNF-alfa due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in sCRP due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)
Change in cortisol due to any treatment (Anakinra vs. saline).	Blood sampling	7 to 9 days (change between study day 1 and study day 2)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Marc Y Donath, MD, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 3, 2017

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimate): September 27, 2016

Study Record Updates

• Last Update Posted (Actual): January 29, 2018
• Last Update Submitted That Met QC Criteria: January 25, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Fatigue; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: EKNZ BASEC 2016-00816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO