Summary of Study ST002857
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 PR001789. The data can be accessed directly via it's Project DOI: 10.21228/M8G43R 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.
| Study ID | ST002857 |
| Study Title | Intracerebroventricular Transplantation of Foetal Allogeneic Neural Stem Cells in Patients with Secondary Progressive Multiple Sclerosis (hNSC-SPMS): a phase I dose-escalation clinical trial - Metabolomics Analysis of Human CSF |
| Study Summary | This is an open-label, first-in-human, dose-escalation phase I study (NCT03282760, EudraCT2015‐004855‐37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of progressive multiple sclerosis. We report the analysis of 1 year of data from the first cohort of 15 patients from two trial sites that received increasing numbers of allogeneic hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed over the 12-month follow-up. Participants displayed stability of clinical and laboratory parameters, as well as lesion load and activity at the brain MRIs, compared to study entry. Longitudinal metabolomics and lipidomics analyses of cerebrospinal fluid and serum from these patients identified time and dose-dependent responses, with increased levels of free fatty acids and acylcarnitines in the CSF, especially at the highest dose of injected hNSCs at the one-year follow-up time point. Finally, a significant inverse correlation was found between the highest dose of injected hNSCs and the smaller parenchymal brain volume change (PBVC; Spearman’s rho= -0.7, p= 0.03), clinical covariates that correlated with CSF levels of free fatty acids, acyl-carnitines, oxylipins, conjugated bile acids and purine breakdown and deamination products, such as hypoxanthine. The absence of AEs and the stability of functional and structural outcomes is reassuring in terms of risks and represent a main milestone to rigorously address the challenges for the safe translation of key principles of stem cell biology into effective regenerative medicines. |
| Institute | University of Colorado Denver |
| Department | Department of Biochemistry and Molecular Genetics |
| Laboratory | Angelo D’Alessandro |
| Last Name | Stephenson |
| First Name | Daniel |
| Address | Research 1 South L18-1303 12801 E. 17th Ave., Aurora, Colorado, 80045, USA |
| daniel.stephenson@cuanschutz.edu | |
| Phone | 303-724-3339 |
| Submit Date | 2023-09-08 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-09-27 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004679 | AN004680 | AN004681 | AN004682 | AN004683 |
|---|---|---|---|---|---|
| Analysis type | MS | MS | MS | MS | MS |
| Chromatography type | Reversed phase | Reversed phase | Reversed phase | Reversed phase | Reversed phase |
| Chromatography system | Thermo Vanquish | Thermo Vanquish | Thermo Vanquish | Thermo Vanquish | Thermo Vanquish |
| Column | Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) | Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) | Phenomenex Kinetex C18 (30 x 2.1mm, 1.7um) | Phenomenex Kinetex C18 (30 x 2.1mm, 1.7um) | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| MS Type | ESI | ESI | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Orbitrap Exploris 120 | Thermo Orbitrap Exploris 120 | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE | NEGATIVE | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area | Peak area | Peak area | Peak area |
Chromatography:
| Chromatography ID: | CH003521 |
| Chromatography Summary: | Metabolomics Positive Mode |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0 min - 0.45 ml/min - 5% B, 0.5 min - 0.45ml/min - 5% B, 1.1 min - 0.45ml/min - 95% B, 2.75 min - 0.45ml/min - 95% B, 3 min - 0.45ml/min - 5% B, 5min - 0.45ml/min - 5%B |
| Flow Rate: | 0.45 ml/min |
| Solvent A: | 0.1% Formic Acid in Water |
| Solvent B: | 0.1% Formic Acid in ACN |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003522 |
| Chromatography Summary: | Metabolomics Negative Mode |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0 min - 0.45 ml/min - 0% B, 0.5 min - 0.45ml/min - 0% B, 1.1 min - 0.45ml/min - 100% B, 2.75 min - 0.45ml/min - 100% B, 3 min - 0.45ml/min - 0% B, 5min - 0.45ml/min - 0%B |
| Flow Rate: | 0.45 ml/min |
| Solvent A: | 5% ACN 95% Water 1mM Ammonium Acetate |
| Solvent B: | 95% ACN 5% Water 1mM Ammonium Acetate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003523 |
| Chromatography Summary: | Lipidomics Negative |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (30 x 2.1mm, 1.7um) |
| Column Temperature: | 50 |
| Flow Gradient: | 0 min - 0.3ml/min - 10%B, 3 min - 0.3ml/min - 95%B, 4.2min - 0.3ml/min -95%B, 4.3min - 0.45ml/min - 10%B, 4.9min - 0.4ml/min - 10%B, 5 min - 0.3ml/min 10%B |
| Flow Rate: | 0.3-.45ml/min |
| Solvent A: | 75:25 H2O:ACN 5mM NH4OAc |
| Solvent B: | 90:10 iPrOH:ACN 5mM NH4OAc |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003524 |
| Chromatography Summary: | Lipidomics Positive |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (30 x 2.1mm, 1.7um) |
| Column Temperature: | 50 |
| Flow Gradient: | 0 min - 0.3ml/min - 30%B, 3 min - 0.3ml/min - 100%B, 4.2min - 0.3ml/min -100%B, 4.3min - 0.4ml/min - 30%B, 4.9min - 0/4ml/min - 30%B, 5 min - 0.3ml/min 30%B |
| Flow Rate: | 0.3-.4ml/min |
| Solvent A: | 75:25 H2O:ACN 5mM NH4OAc |
| Solvent B: | 90:10 iPrOH:ACN 5mM NH4OAc |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003525 |
| Chromatography Summary: | Oxylipin Method |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 60 |
| Flow Gradient: | 0min - 0.35ml/min - 0%B, 0.5min - 0.35ml/min - 25%B, 1min - 0.35ml/min - 25%B, 2.5min - 0.35ml/min 40%B, 2.6min -0.35ml/min 55%B, 4.5min - 0.35ml/min - 70%B, 4.6min - 0.35ml/min - 100%B, 6min - 0.35ml/min - 100%B, 6.1min - 0.35ml/min - 0%B, 7min - 0.35ml/min 0%B |
| Flow Rate: | .35ml/min |
| Solvent A: | 20:80:0.02 ACN:Water:Formic Acid |
| Solvent B: | 20:80:0.02 ACN:IPA:Formic Acid |
| Chromatography Type: | Reversed phase |
