Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day). During bed rest, participants will be given 1 gram of metformin two times a day (morning and evening). This dosage and frequency will occur during four consecutive days of bed rest.

Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group. During bed rest, participants will be given the same amount of pills and given at the same time of day (morning and evening) as the experimental group. This strategy will occur during four consecutive days of bed rest.

Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day). These participants will not participate in the bed rest portion of the protocol.

Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group. These participants will not participate in the bed rest portion of the protocol.

Muscle Atrophy

Insulin Resistance

A clinical oral dose of Metformin will be given to participant daily during bed rest

Metformin (Bed Rest)

Placebo-comparator. The same quantity of non-active tablets will be given at the same time of day as the Metformin treatment group

Placebo (Bed Rest)

A clinical oral dose of Metformin will be given to participant daily during a two week run-in period only.

Metformin (2 week run-in only)

Placebo-comparator. The same quantity of non-active tablets will be given at the same time of day as the Metformin 2 week run-in treatment group.

Placebo (2 week run-in only)

University of Utah

Role of Metformin on Muscle Health of Older Adults

Metformin to Prevent Inactivity-induced Loss of Muscle Health During Aging

Change in muscle size from baseline to 5-days of bed rest (determined from MRI)

Micah Drummond

Assistant Professor

drug and placebo will be encapsulated therefore concealing the participant, investigator and outcome assessor to group assignment.

Patients with Farber disease or high-grade suspicion for Farber disease

For the development of the new biomarkers using the technique of Mass-spectometry, a blood sample will be taken via using a dry blood spot filter card. To proof the correct Farber diagnosis in those patients where up to the enrolment in the study no genetic testing has been done, sequencing of Farber will be done. The analyses will be done at: Centogene AG Am Strande 7 18055 Rostock Germany

Farber's Lipogranulomatosis

Ceramidase Deficiency

Hepatomegaly

Splenomegaly

Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine

Children Hospital, Faculty of Medicine, Cairo University

Centogene AG

Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)

Biomarker for Farber Disease (BioFarber)

Biomarker for Farber Disease - An International, Multicenter, Epidemiological Protocol

Next-Generation Sequencing (NGS) of the ASAH1 gene will be performed. The mutation will be confirmed by Sanger sequencing.

The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker.

ceramide/atrophy

Role of Metformin on Muscle Health of Older Adults

Biomarker for Farber Disease (BioFarber)

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