Summary of Study ST002432

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001565. The data can be accessed directly via it's Project DOI: 10.21228/M8DD8S This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002432
Study TitleMetabolic impacts of metformin to seasonal influenza vaccination: a pilot study of drug interaction with the immune response
Study SummaryWe report here a double-blinded pilot study of seasonal influenza vaccination, where half of the participants received daily metformin administration. Global metabolomics was measured in the plasma samples at six timepoints. Metformin signatures were successfully identified in the metabolomics data. Statistically significant metabolite features were found both for the vaccination effect and for the drug-vaccine interactions.
Institute
The Jackson Laboratory for Genomic Medicine
LaboratoryShuzhao Li Lab
Last NameSiddiqa
First NameAmnah
Address10 Discovery dr, Farmington, CT 06032
Emailamnah.siddiqa@jax.org
Phone4049187223
Submit Date2023-01-04
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-01-20
Release Version1
Amnah Siddiqa Amnah Siddiqa
https://dx.doi.org/10.21228/M8DD8S
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001565
Project DOI:doi: 10.21228/M8DD8S
Project Title:Metabolic impacts of metformin to seasonal influenza vaccination: a pilot study of drug interaction with the immune response
Project Summary:We report here a double-blinded pilot study of seasonal influenza vaccination, where half of the participants received daily metformin administration. Global metabolomics was measured in the plasma samples at six timepoints. Metformin signatures were successfully identified in the metabolomics data. Statistically significant metabolite features were found both for the vaccination effect and for the drug-vaccine interactions.
Institute:The Jackson Laboratory For Genomic Medicine
Laboratory:Shuzhao Li Lab
Last Name:Siddiqa
First Name:Amnah
Address:10 Discovery Drive , Farmington, CT 06032
Email:amnah.siddiqa@jax.org
Phone:4049187223

Subject:

Subject ID:SU002521
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Visit Treatment
SA242997YW_20201206_163.mzMLV1 Metformin
SA242998YW_20201206_135.mzMLV1 Metformin
SA242999YW_20201206_101.mzMLV1 Metformin
SA243000YW_20201206_227.mzMLV1 Metformin
SA243001YW_20201206_072.mzMLV1 Metformin
SA243002YW_20201206_089.mzMLV1 Metformin
SA243003YW_20201206_199.mzMLV1 Metformin
SA243004YW_20201206_071.mzMLV1 Metformin
SA243005YW_20201210_163.mzMLV1 Metformin
SA243006YW_20201210_135.mzMLV1 Metformin
SA243007YW_20201210_199.mzMLV1 Metformin
SA243008YW_20201210_227.mzMLV1 Metformin
SA243009YW_20201206_115.mzMLV1 Metformin
SA243010YW_20201206_090.mzMLV1 Metformin
SA243011YW_20201206_136.mzMLV1 Metformin
SA243012YW_20201210_164.mzMLV1 Metformin
SA243013YW_20201210_136.mzMLV1 Metformin
SA243014YW_20201210_102.mzMLV1 Metformin
SA243015YW_20201210_200.mzMLV1 Metformin
SA243016YW_20201210_228.mzMLV1 Metformin
SA243017YW_20201210_090.mzMLV1 Metformin
SA243018YW_20201210_072.mzMLV1 Metformin
SA243019YW_20201206_102.mzMLV1 Metformin
SA243020YW_20201206_164.mzMLV1 Metformin
SA243021YW_20201206_200.mzMLV1 Metformin
SA243022YW_20201206_228.mzMLV1 Metformin
SA243023YW_20201210_116.mzMLV1 Metformin
SA243024YW_20201210_115.mzMLV1 Metformin
SA243025YW_20201206_116.mzMLV1 Metformin
SA243026YW_20201210_101.mzMLV1 Metformin
SA243027YW_20201210_089.mzMLV1 Metformin
SA243028YW_20201210_071.mzMLV1 Metformin
SA243029YW_20201210_174.mzMLV1 Placebo
SA243030YW_20201210_038.mzMLV1 Placebo
SA243031YW_20201210_173.mzMLV1 Placebo
SA243032YW_20201210_194.mzMLV1 Placebo
SA243033YW_20201206_193.mzMLV1 Placebo
SA243034YW_20201206_245.mzMLV1 Placebo
SA243035YW_20201210_246.mzMLV1 Placebo
SA243036YW_20201206_235.mzMLV1 Placebo
SA243037YW_20201210_236.mzMLV1 Placebo
SA243038YW_20201206_037_20201208155945.mzMLV1 Placebo
SA243039YW_20201210_245.mzMLV1 Placebo
SA243040YW_20201210_235.mzMLV1 Placebo
SA243041YW_20201206_173.mzMLV1 Placebo
SA243042YW_20201206_140.mzMLV1 Placebo
SA243043YW_20201210_058.mzMLV1 Placebo
SA243044YW_20201210_037.mzMLV1 Placebo
SA243045YW_20201210_193.mzMLV1 Placebo
SA243046YW_20201206_057.mzMLV1 Placebo
SA243047YW_20201210_057.mzMLV1 Placebo
SA243048YW_20201206_139.mzMLV1 Placebo
SA243049YW_20201210_139.mzMLV1 Placebo
SA243050YW_20201206_058.mzMLV1 Placebo
SA243051YW_20201210_140.mzMLV1 Placebo
SA243052YW_20201206_174.mzMLV1 Placebo
SA243053YW_20201206_194.mzMLV1 Placebo
SA243054YW_20201206_038_20201208160505.mzMLV1 Placebo
SA243055YW_20201206_246.mzMLV1 Placebo
SA243056YW_20201206_236.mzMLV1 Placebo
SA243057YW_20201206_220.mzMLV2 Metformin
SA243058YW_20201210_087.mzMLV2 Metformin
SA243059YW_20201206_088.mzMLV2 Metformin
SA243060YW_20201210_158.mzMLV2 Metformin
SA243061YW_20201206_067.mzMLV2 Metformin
SA243062YW_20201206_158.mzMLV2 Metformin
SA243063YW_20201206_107_20201210165216.mzMLV2 Metformin
SA243064YW_20201210_094.mzMLV2 Metformin
SA243065YW_20201206_087.mzMLV2 Metformin
SA243066YW_20201206_208.mzMLV2 Metformin
SA243067YW_20201206_134.mzMLV2 Metformin
SA243068YW_20201210_067.mzMLV2 Metformin
SA243069YW_20201206_219.mzMLV2 Metformin
SA243070YW_20201210_107.mzMLV2 Metformin
SA243071YW_20201210_093.mzMLV2 Metformin
SA243072YW_20201210_108.mzMLV2 Metformin
SA243073YW_20201206_108_20201210165738.mzMLV2 Metformin
SA243074YW_20201206_207.mzMLV2 Metformin
SA243075YW_20201206_093.mzMLV2 Metformin
SA243076YW_20201210_088.mzMLV2 Metformin
SA243077YW_20201206_133.mzMLV2 Metformin
SA243078YW_20201206_094.mzMLV2 Metformin
SA243079YW_20201210_068.mzMLV2 Metformin
SA243080YW_20201206_068.mzMLV2 Metformin
SA243081YW_20201210_134.mzMLV2 Metformin
SA243082YW_20201206_157.mzMLV2 Metformin
SA243083YW_20201210_220.mzMLV2 Metformin
SA243084YW_20201210_219.mzMLV2 Metformin
SA243085YW_20201210_133.mzMLV2 Metformin
SA243086YW_20201210_157.mzMLV2 Metformin
SA243087YW_20201210_208.mzMLV2 Metformin
SA243088YW_20201210_207.mzMLV2 Metformin
SA243089YW_20201206_248.mzMLV2 Placebo
SA243090YW_20201210_191.mzMLV2 Placebo
SA243091YW_20201210_192.mzMLV2 Placebo
SA243092YW_20201210_043.mzMLV2 Placebo
SA243093YW_20201210_044.mzMLV2 Placebo
SA243094YW_20201206_182.mzMLV2 Placebo
SA243095YW_20201210_182.mzMLV2 Placebo
SA243096YW_20201210_142.mzMLV2 Placebo
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Collection:

Collection ID:CO002514
Collection Summary:EDTA-treated whole blood was immediately centrifuged and the resultant plasma was stored at -80˚C until analyses. Plasma metabolites extraction was carried out by protein precipitation technique using extraction solvent, acetonitrile:methanol (8:1, v/v) containing 0.1% formic acid. All samples were vortexed and incubated with shaking at 1000 rpm for 10 min at 4˚C followed by centrifugation at 4˚ C for 15 min at 15,000 rpm. The supernatant was transferred into mass spec vials and 2 micro liter injected into UHPLC-MS.
Sample Type:Blood (plasma)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002533
Treatment Summary:This pilot study is a double-blinded placebo-controlled trial in men and women over the age of 65 years. Subjects were screened rigorously for eligibility. Study exclusion criteria included the following: any unstable medical conditions or severe co-morbidities (severe COPD, severe congestive heart failure, advanced neurological disorders, etc), contraindications for metformin (severe renal or liver impairment), contraindication for flu vaccine (history of Guillain-Barre syndrome post vaccination or allergic to component of vaccine), immunosuppressive disorders, immunosuppressive medications, and active cancer. Importantly, participants were excluded if they were prediabetic or diabetic (HbA1c ≥ 5.7%) to avoid any confounding impact of metformin on diabetes status. Eligible participants were randomized to metformin (final dose 1500mg extended release (ER)/day) or placebo treatment. To limit gastrointestinal issues per current metformin label recommendations, participants started with 1 tablet a day for week 1 (500mg metformin ER/day or placebo), then 2 tablets a day for week 2 (1000mg metformin ER or placebo), and finally 3 tablets a day for week 3 until the completion of the study (1500mg metformin ER or placebo). Fifteen subjects (n=8 metformin, n=7 placebo) were randomized and completed the study on treatment with no differences in basic characteristics at baseline (placebo: 74.71±2.45 years old, 3 males, BMI: 27.31±1.68; metformin: 74.13±2.42 years old, 5 males, BMI: 26.43±1.47). All participants were vaccinated with Fluzone high-dose trivalent flu vaccine (Sanofi Pasteur Inc., Swiftwater, PA) after ~70 days of treatment. Blood was drawn via standard venipuncture into EDTA-treated vacutainers prior to treatment (Day 0), prior to vaccination (~day 35 and ~day 70), and 7, ~35, and ~70 days post vaccination. The study protocol was approved by the Institutional Review Board at the University of Connecticut Health Center (UCHC) and registered at ClinicalTrials.gov (NCT03996538). All study participants provided written informed consent to participate in the study.

Sample Preparation:

Sampleprep ID:SP002527
Sampleprep Summary:The plasma samples were thawed in ice. Metabolites extraction were carried out by protein precipitation using extraction solvent, acetonitrile:methanol (8:1, v/v) containing 0.1% formic acid and isotope labelled Trimethyl-13C3]-caffeine, [13C5]-L-glutamic acid, [15N2]-Uracil, [15N,13C5]-L-methionine, [13C6]-D-glucose and [15N]-L-tyrosin as spike-in controls. 30 μl of plasma was taken and 60 μl of extraction solvent was added. All samples were vortexed and incubated with shaking at 1000 rpm for 10 min at 4°C followed by centrifugation at 4°C for 15 min at 15,000 rpm. The supernatant was transferred into mass spec vials and 2 μl injected into UHPLC-MS.

Combined analysis:

Analysis ID AN003959 AN003960 AN003961 AN003962
Analysis type MS MS MS MS
Chromatography type HILIC HILIC Reversed phase Reversed phase
Chromatography system Thermo Scientific Transcend Duo LX-2 UHPLC Thermo Scientific Transcend Duo LX-2 UHPLC Thermo Scientific Transcend Duo LX-2 UHPLC Thermo Scientific Transcend Duo LX-2 UHPLC
Column Thermo Accucore 150 Amide (50 x 2.1mm, 2.6um) Thermo Accucore 150 Amide (50 x 2.1mm, 2.6um) Thermo Hypersil GOLD RP (50 x 2.1mm, 3um) Thermo Hypersil GOLD RP (50 x 2.1mm, 3um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Orbitrap ID-X Tribrid Thermo Orbitrap ID-X Tribrid Thermo Orbitrap ID-X Tribrid Thermo Orbitrap ID-X Tribrid
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE
Units m/z m/z m/z m/z

Chromatography:

Chromatography ID:CH002929
Instrument Name:Thermo Scientific Transcend Duo LX-2 UHPLC
Column Name:Thermo Accucore 150 Amide (50 x 2.1mm, 2.6um)
Column Temperature:45
Flow Gradient:0.55 ml/min: 0-0.1 min: 0% B, 0.10-5.0 min: 98% B, and 5 min for cleaning and equilibration of column.
Flow Rate:0.55 ml/min
Solvent A:95% acetonitrile/5% water; 0.1% acetic acid; 10 mM ammonium acetate
Solvent B:50% acetonitrile/50% water; 0.1% acetic acid; 10 mM ammonium acetate
Chromatography Type:HILIC
  
Chromatography ID:CH002930
Instrument Name:Thermo Scientific Transcend Duo LX-2 UHPLC
Column Name:Thermo Hypersil GOLD RP (50 x 2.1mm, 3um)
Column Temperature:45
Flow Gradient:0-0.1 min: 0% B, 0.10-1.9 min: 60% B, 1.9-5.0 min: 98% B, and 5 min cleaning and column equilibration
Flow Rate:0.4 ml/min
Solvent A:10 mM ammonium acetate in acetonitrile:water (95:5, v/v) with 0.1% acetic acid
Solvent B:10 mM ammonium acetate in acetonitrile:water (50:50, v/v) with 0.1% acetic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS003694
Analysis ID:AN003959
Instrument Name:Thermo Orbitrap ID-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Asari was used for data processing
Ion Mode:POSITIVE
  
MS ID:MS003695
Analysis ID:AN003960
Instrument Name:Thermo Orbitrap ID-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Asari was used for data processing
Ion Mode:NEGATIVE
  
MS ID:MS003696
Analysis ID:AN003961
Instrument Name:Thermo Orbitrap ID-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Asari was used for data processing
Ion Mode:POSITIVE
  
MS ID:MS003697
Analysis ID:AN003962
Instrument Name:Thermo Orbitrap ID-X Tribrid
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Asari was used for data processing
Ion Mode:NEGATIVE
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