Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)Phase 1MASSNCT02427178
MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
A Phase 1 study testing Hematopoietic Allogeneic Stem Cells in people with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE), run by Michio Hirano, MD.
Trial summary
The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. The stem cell transplant is called AHSCT (for "allogeneic hematopoetic stem cell transplantation"). The rare disease is called MNGIE (for "Mitochondrial NeuroGastroIntestinal Encephalomyopathy"). Read more about this study
- Who is it for?
- Ages 5 to 55 years
- Conditions the study is for
- Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
- What is being tested?
- Hematopoietic Allogeneic Stem Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2015to Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Homozygous or compound heterozygous mutations in the TYMP gene
- Plasma thymidine level >3micromole/L
- Plasma deoxyuridine >7.5 micromole/L
- 5 to 55 years of age
- Appropriate stem cell donor (HLA 10/10 matched)
- Karnofsky performance of at least 55
Who cannot join
- Severe cognitive impairment
- Severe psychiatric illness
- Moderate to severe lung disease
- Prior episode of peritonitis due to perforated diverticula
- Prior episode of intestinal pseudo-obstruction
- Moderate to severe hepatopathy
Show all 13Show fewer
- Moderate to severe diabetes Mellitus
- Moderate to severe cardiomyopathy
- Moderate to severe nephropathy
- Pregnancy or planning to become pregnant during study
- Hypersensitivity to E.coli derived products
- HIV disease
- Positive to anti-donor HLA DP
About this study
Official title: MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study
The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. The stem cell transplant is called AHSCT (for "allogeneic hematopoetic stem cell transplantation"). The rare disease is called MNGIE (for "Mitochondrial NeuroGastroIntestinal Encephalomyopathy"). Patients with MNGIE will be transplanted with stem cells from an individual who is human leukocyte antigen (HLA) 10/10 matched. The purpose of the transplant is the production of thymidine phosphorylase.
Read the detailed description
Patients who have been identified as having MNGIE by genetic testing and/or reduced thymidine phosphorylase levels will be considered for this study. The study team physician will evaluate the condition of the patient and determine if they are eligible. An HLA matched donor is necessary for transplantation. If a suitable donor is found the transplant process can proceed. The patient receives immunosuppressive therapy ( 1 week in the hospital) with subsequent IV transfer of stem cells from the donor. The patient remains in the hospital for approximately 1 month to monitor the transplant. The patient is required to attend research visits at days 0, 100, 6m, 18m and 24 m.
- Being tested
- Hematopoietic Allogeneic Stem Cells
- Keywords
- Allogeneic Hematopoietic Stem Cell Transplantation, MNGIE, Stem Cell transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic Allogeneic Stem CellsBiological
HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).
| Study group | Role | What they receive |
|---|---|---|
| Open label | Experimental | Hematopoietic allogeneic stem cells will be transplanted:
HLA testing will be performed on potential stem cell donors. HLA 10/10 matched donors are eligible, however there are additional criteria that will be applied to determine an acceptable donor. Patients will receive 2 X10 6 CD34 cells/kg weight. Receives: Biological: Hematopoietic Allogeneic Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
neutrophil count (cells/L)
engraftment success
Measured: 42 days
Secondary outcomes (4)
number of patient survival days
is the patient al
Measured: 100 days
chimerism percentage
percent of donor cell chimerism at 100 days
Measured: 100 days
micromole/l dUrd
level of deoxyuridine
Measured: 100 days
micromole Thd
level of thymidine
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2015 (estimated)
- Study startMar 2015 (estimated)
- Primary completionJun 2022 (estimated)
- Study completionJun 2023 (estimated)
Why it stopped: Poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michio Hirano, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Cornell University, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor-investigator, Michio Hirano, MD, Columbia University
- Investigators
- Michio Hirano, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02427178
- Sponsor's protocol ID
- AAAI1718
- Other IDs
- U54NS078059
- Acronym
- MASS
- Status last verified
- Jul 2022
- First submitted
- 10 Feb 2015
- Last updated
- 1 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: When applicable, we will submit a manuscript describing the results
Publications
Halter J, Schupbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krahenbuhl S, Lehmann T, Mandel H, Marti R, Mattle H, Orchard K, Savage D, Sue CM, Valcarcel D, Gratwohl A, Hirano M. Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant. 2011 Mar;46(3):330-337. doi: 10.1038/bmt.2010.100. Epub 2010 May 3.
PubMed 20436523Marti R, Lopez LC, Hirano M. Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Methods Mol Biol. 2012;837:121-33. doi: 10.1007/978-1-61779-504-6_8.
PubMed 22215544Hirano M, Nishino I, Nishigaki Y, Marti R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med. 2006;45(19):1103. doi: 10.2169/internalmedicine.45.6064. Epub 2006 Nov 1. No abstract available.
PubMed 17077575Valentino ML, Marti R, Tadesse S, Lopez LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett. 2007 Jul 24;581(18):3410-4. doi: 10.1016/j.febslet.2007.06.042. Epub 2007 Jun 27.
PubMed 17612528
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study
- ClinicalTrials.gov ID
- NCT02427178
- Acronym / sponsor ID
- MASS / AAAI1718
- Keywords
- Allogeneic Hematopoietic Stem Cell Transplantation, MNGIE, Stem Cell transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Poor enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Michio Hirano, MDUniversity, hospital or other
- Collaborators
- Cornell University, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Mar 2015 (estimated)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 27 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. The stem cell transplant is called AHSCT (for "allogeneic hematopoetic stem cell transplantation"). The rare disease is called MNGIE (for "Mitochondrial NeuroGastroIntestinal Encephalomyopathy"). Patients with MNGIE will be transplanted with stem cells from an individual who is human leukocyte antigen (HLA) 10/10 matched. The purpose of the transplant is the production of thymidine phosphorylase.
Detailed description
Patients who have been identified as having MNGIE by genetic testing and/or reduced thymidine phosphorylase levels will be considered for this study. The study team physician will evaluate the condition of the patient and determine if they are eligible. An HLA matched donor is necessary for transplantation. If a suitable donor is found the transplant process can proceed. The patient receives immunosuppressive therapy ( 1 week in the hospital) with subsequent IV transfer of stem cells from the donor. The patient remains in the hospital for approximately 1 month to monitor the transplant. The patient is required to attend research visits at days 0, 100, 6m, 18m and 24 m.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label | Experimental | Biological: Hematopoietic Allogeneic Stem CellsHematopoietic allogeneic stem cells will be transplanted: HLA testing will be performed on potential stem cell donors. HLA 10/10 matched donors are eligible, however there are additional criteria that will be applied to determine an acceptable donor. Patients will receive 2 X10 6 CD34 cells/kg weight. |
Who may qualify
- Ages
- 5 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Homozygous or compound heterozygous mutations in the TYMP gene
- Plasma thymidine level >3micromole/L
- Plasma deoxyuridine >7.5 micromole/L
- 5 to 55 years of age
- Appropriate stem cell donor (HLA 10/10 matched)
Key exclusion criteria (13 listed)
- Severe cognitive impairment
- Severe psychiatric illness
- Moderate to severe lung disease
- Prior episode of peritonitis due to perforated diverticula
- Prior episode of intestinal pseudo-obstruction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hematopoietic Allogeneic Stem CellsHLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient). | Biological | Open label |
Primary outcome
neutrophil count (cells/L)
Time frame: 42 days
engraftment success
4 secondary outcomes
number of patient survival days
Time frame: 100 days
chimerism percentage
Time frame: 100 days
micromole/l dUrd
Time frame: 100 days
micromole Thd
Time frame: 100 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
- Background: PubMed 20436523Halter J, Schupbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krahenbuhl S, Lehmann T, Mandel H, Marti R, Mattle H, Orchard K, Savage D, Sue CM, Valcarcel D, Gratwohl A, Hirano M. Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant. 2011 Mar;46(3):330-337. doi: 10.1038/bmt.2010.100. Epub 2010 May 3.
- Background: PubMed 22215544Marti R, Lopez LC, Hirano M. Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Methods Mol Biol. 2012;837:121-33. doi: 10.1007/978-1-61779-504-6_8.
- Background: PubMed 17077575Hirano M, Nishino I, Nishigaki Y, Marti R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med. 2006;45(19):1103. doi: 10.2169/internalmedicine.45.6064. Epub 2006 Nov 1. No abstract available.
- Background: PubMed 17612528Valentino ML, Marti R, Tadesse S, Lopez LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett. 2007 Jul 24;581(18):3410-4. doi: 10.1016/j.febslet.2007.06.042. Epub 2007 Jun 27.
- Individual participant dataSharing planned: Yes. When applicable, we will submit a manuscript describing the results
Related trials for Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
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North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC)
Mitochondrial Disorders, Mitochondrial Genetic Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michio Hirano, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hematopoietic Allogeneic Stem Cells in people with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE), run by Michio Hirano, MD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
neutrophil count (cells/L) (time frame: 42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02427178, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2022.