Role of Interleukin-1 in Postprandial Fatigue - The Cheesecake Study

Role of Interleukin-1 in Postprandial Fatigue - The Cheesecake Study. A Randomized, Double-blind, Single Dose of Anakinra, Placebo-controlled, Cross-over Proof-of-concept Study.

The aim of the study is to investigate, if postprandial fatigue symptoms after ingestion of a high-fat, high-carbohydrate meal are regulated by Interleukin (IL)-1 and can be prevented by inhibition of IL-1 using a single dose injection of a specific IL-1 receptor antagonist.

Study Overview

• Status: Completed
• Conditions: Postprandial Fatigue
• Intervention / Treatment: Drug: Anakinra; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male
• non-smoking
• apparently healthy
• BMI >18 and ≤25 kg/m2
• Age 20-50 years
• 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), sterilization (e.g., tubal ligation or a monogamous relationship with a vasectomized partner), and abstinence.

Exclusion Criteria:

• 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 Anakinra
• Known allergy towards 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 enrollment 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

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anakinra; Anakinra 100mg. Every subject will receive one subcutaneous injection of study drug once during the study, a total of one injection.	Drug: Anakinra; Each subject will receive one single subcutaneous injection of 100mg Anakinra during the study, a total of one injection.; Other Names: Kineret
Placebo Comparator: Placebo; Every study participant will receive a single subcutaneous injection of Placebo once during the study, a total of one injection.	Drug: Placebo; Every subject will receive one single subcutaneous injection of Placebo during the study, a total of one injection.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial fatigue	Fatigue will be assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC) pre-study drug (means 180 minutes before ingestion of the test meal), 30 minutes before ingestion of the test meal and again 30 minutes after ingestion of the test meal. The outcome measure for which data will be presented is the change in fatigue measured 30 minutes before and 30 minutes after ingestion of the test meal in participants receiving kineret vs. placebo. Fatigue will also be assessed before administration of the study drug (180 minutes before test meal) to unravel a possible influence of the study drug itself on fatigue symptoms.	pre-study drug (180 minutes pre-meal), 30 minutes pre-meal and 30 minutes post-meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial depression	Depression will be assessed using the Hospitality Anxiety and Depression Scale - german version (HADS-D) pre-study drug (means 180 minutes before ingestion of the test meal), 30 minutes before ingestion of the test meal and again 30 minutes after ingestion of the test meal. The outcome measure for which data will be presented is the change in depression measured 30 minutes before and 30 minutes after ingestion of the test meal in participants receiving kineret vs. placebo. Depression will also be assessed before administration of the study drug (180 minutes before test meal) to unravel a possible influence of the study drug itself on depression.	pre-study drug (180 minutes pre test meal), 30 minutes pre-meal, 30 minutes post-meal
Postprandial cognitive processing speed	Cognitive processing speed will be assessed using the oral version of the Symbol Digit Modalities Test (SDMT) version A before study drug (means 180 minutes before ingestion of the test meal), version B 30 minutes before ingestion of the test meal and version A 30 minutes after ingestion of the test meal. The outcome measure for which data will be presented is the change in cognitive processing speed measured 30 minutes before and 30 minutes after ingestion of the test meal in participants receiving kineret vs. placebo. Cognitive processing speed will also be assessed before administration of the study drug (180 minutes before test meal) to unravel a possible influence of the study drug itself on depression. Version A and B will be used alternately to prevent a learning effect in this test.	pre-study drug (180 minutes before test meal), 30 minutes pre-meal, 30 minutes post-meal
Insulin, C-peptide, Glucose		-180, -10 and 0 minutes before ingestion of the test meal; 5, 15, 30, 60, 90, 120, 180 and 240 minutes after full ingestion of the test meal
Gut hormones and inflammatory markers		-180, -10 and 0 minutes before ingestion of the test meal; 5, 15, 30, 60, 90, 120, 180 and 240 minutes after full ingestion of the test meal

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Marc Y Donath, Prof., Univesity Hospital Basel

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 4, 2013
• First Submitted That Met QC Criteria: March 11, 2013
• First Posted (Estimate): March 13, 2013

Study Record Updates

• Last Update Posted (Estimate): December 17, 2014
• Last Update Submitted That Met QC Criteria: December 16, 2014
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Fatigue
• Additional Relevant MeSH Terms: Fatigue; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: EK 303/12