Multiple SclerosisPhase 4NCT03092544
Investigating Indirect Mechanism of Neuroprotection of Tecfidera® (Dimethyl Fumarate) in RRMS and Progressive Patients
A Phase 4 study testing dimethyl fumarate in people with Multiple Sclerosis, run by Multiple Sclerosis Center of Northeastern New York at 1 site in United States.
Trial summary
The purposes of this study is to identify types of bacteria that reside in the intestine of healthy individuals and compare them to individuals with Multiple Sclerosis (MS). There has been a lot of research in other autoimmune diseases which has demonstrated the importance of stomach "gut" bacteria because it has an… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- dimethyl fumarate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Dec 2018
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Male or female subject, age 18-65 (inclusive) at the time of informed consent, with a confirmed diagnosis of multiple sclerosis and meeting multiple sclerosis patient population as specified in section 4/ study design/multiple sclerosis population of this protocol.
- Subject has the ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Expanded Disability Status Scale (EDSS) score between 0 and 7, inclusive, at screen.
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Normal control volunteer meeting age and co-inhabitant criteria as specified in section 4/ study design/normal control population of this protocol.
- Subject has the ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
Who cannot join
- General and Medical History Exclusions
- A MS relapse, as determined by the investigator, that occurred within 90 days prior to screen or the subject has not stabilized from a previous relapse prior to screen visit.
- Current smoker
- Any contraindication to having a brain MRI (e.g. pacemaker, MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed) or contraindication for administration of gadolinium-contrast agents.
- Clinically significant brain MRI findings other than those related to MS, as judged by the investigator, at screen.
- Any contraindications to having a Lumbar puncture (LP) (i.e. Aspirin (ASA) greater than 325mg/day, Coumadin, Plavix, decreased platelet count) as determined by the investigator.
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- History of Chronic Urinary Tract Infections, Irritable Bowel Syndrome, Inflammatory Bowel Disease, Diabetes Mellitus or vascular disease as determined by history and investigator decision
- Evidence or history of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, diabetes mellitus or others) with the exception of MS.
- History of or current clinically relevant gastrointestinal bleeding or other gastrointestinal diseases or processes that may interfere with the analysis of stool samples per protocol.
- Any sign of chronic active infection (e.g. urinary tract infection (UTI), bronchitis, hepatitis and tuberculosis) except for those requiring topical medication for treatment (e.g., athletes foot), or screening laboratory evidence consistent with a significant chronic active acute infection requiring systemic treatment. This must be resolved before treatment may commence, (e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections).
- Pregnant females; breastfeeding females and/or males of childbearing potential; females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of dimethyl fumarate use in this protocol. For females of childbearing potential in the dimethy fumarate population; a positive pregnancy test at anytime within the protocol.
- Known Positive HIV antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody tests indicative of present or prior infection.
- Any abnormal hematology values or clinical chemistry values judged by the Investigator or Sponsor as clinically significant.
- Positive purified protein derivative (PPD) skin test or positive quantiferon (QTFN) at screen visit or know history of active tuberculosis not adequately treated.
- Any malignancy within 5 years, except for basal or Squamous cell skin lesions which have been surgically excised, with no evidence of metastasis.
- Any clinical, CSF or MRI evidence for Progressive multifocal leukoencephalopathy (PML), from historical MRI or results of the screen MRI.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Subjects participating in or expecting to participate in other interventional clinical trials.
- Inability or unwillingness to record online dietary questionnaire information as required by protocol
- History of drug or alcohol abuse (as defined by the investigator) within 2 years prior to screen.
- Previous Exposure to dimethy fumarate for disease management at any time in the past.
- Treatment with methylprednisolone or other systemic corticosteroid for multiple sclerosis relapse or otherwise within 30 days prior to day one of IP administration.
- Treatment with multiple sclerosis disease modifying therapies as follows:
- Beta interferons (interferon beta-1a [Avonex® or Rebif®] or interferon beta-1b [Betaseron®], or glatiramer [Copaxone®] within 6 weeks prior to Baseline.
- Fingolimod (Gilenya®), Teriflunomide (Aubagio®) or washout with accelerated elimination and verification of zero serum levels of teriflunomide prior to day one baseline)
- Tysabri® (Natalizumab)
- within 6 months prior to screen OR
- one month prior to screen if subject has a positive Nabs to Tysabri®
- Treatment within the past 5 years or current treatment with any of the following agents: cyclosporine, cladribine, that are immunosuppressive (e.g. rituximab, etanercept, cellcept, others), murine protein, T-cell vaccination, plasmapheresis, IV immunoglobulin (IgG) or stem cell transplantation prior to screen.
- Receipt of any non-live vaccine within the previous 14 days or live vaccine within 30 days prior to first dose of investigational product (IP).
- Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication, whichever is longer.
- Use of antibiotics for any reason within 3 months of screen.
- General and Medical History Exclusions
- Current Smoker
- Any contraindications to having a lumbar puncture (LP) (i.e. ASA greater than 325mg/day, Coumadin, Plavix, decreased platelet count) as determined by the investigator.
- History of Chronic Urinary Tract Infections, Irritable Bowel Syndrome, Inflammatory Bowel Disease, Diabetes Mellitus or vascular disease as determined by history and investigator decision.
- Evidence or history of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, diabetes mellitus or others) including the diagnosis of MS or MS symptomatology.
- History of or current clinically relevant gastrointestinal bleeding or other gastrointestinal diseases or processes that may interfere with the analysis of stool samples per protocol.
- Any malignancy within 5 years, except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis.
- Any sign of chronic active infection (e.g. UTI, bronchitis, hepatitis and tuberculosis) except for those requiring topical medication for treatment (e.g., athletes foot), or screening laboratory evidence consistent with a significant chronic active acute infection requiring systemic treatment. This must be resolved before treatment may commence, (e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections).
- Pregnant or breastfeeding females
- Known Positive HIV antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody tests indicative of present or prior infection.
- Any abnormal hematology values or clinical chemistry values judged by the Investigator or Sponsor as clinically significant at baseline visit.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormalities that may increase the risk associated with study participation or investigational product administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Inability or unwillingness to record online dietary questionnaire information as required by protocol.
- History of drug or alcohol abuse (as defined by the investigator) within 2 years prior to baseline.
Trial locations and contacts
1 site in 1 country.
United States1 site
Multiple Sclerosis Center of Northeastern New York
Latham, New York, 12110
About this study
The purposes of this study is to identify types of bacteria that reside in the intestine of healthy individuals and compare them to individuals with Multiple Sclerosis (MS). There has been a lot of research in other autoimmune diseases which has demonstrated the importance of stomach "gut" bacteria because it has an important relationship with the immune system, but this has never been studied in MS patients. In this study investigators aim to show differences in the gut bacteria between healthy individuals and those with MS, to provide a basis for future research studying how diet can affect MS through its effects on the "gut" bacteria.
Additionally, this study will be looking at the effects of dimethyl fumarate on cerebrospinal fluid, plasma and MRI in MS patients taking dimethyl fumarate as compared to those with MS not on dimethyl fumarate or other disease modifying therapy and those who do not have MS (normal controls).
- Conditions
- Multiple Sclerosis
- Being tested
- dimethyl fumarate
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dimethyl fumarateDrug
Also called Tecfidera,
Active drug
| Study group | Role | What they receive |
|---|---|---|
| RRMS on therapy | Active comparator | 18 subjects with a diagnosis of Relapsing Remitting (RRMS) ages 18-55, that are scheduled to begin on dimethyl fumarate Receives: Drug: dimethyl fumarate |
| SPMS on therapy | Active comparator | 18 subjects with a diagnosis of Secondary Progressive (SPMS) ages 25-65 without clinical or MRI evidence of relapse in two years that are scheduled to begin on dimethyl fumarate Receives: Drug: dimethyl fumarate |
| SPMS not on therapy | No intervention | 18 subjects with a diagnosis of SPMS ages 25-65 without clinical or MRI evidence of relapse in two years, that are NOT scheduled to begin on dimethyl fumarate |
| Normal Control 1 | No intervention | 10 normal controls (younger cohort, mean age 38) |
| Normal Control 2 | No intervention | 10 normal controls (younger cohort, mean age 58) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics
Measured: change from baseline at 6 months treatment with dimethyl fumarate
Change in cerebrospinal (CSF) samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics
Measured: change from baseline at 6 months treatment with dimethyl fumarate
change in levels of neurofilament( NFL) in RRMS patients
Measured: at baseline and after 6 months of therapy
change in levels of ceramide sphyngosine and other lipid species in samples collected from patients before and after therapy in CSF samples in RRMS patients
Measured: at baseline and 6 months of therapy
changes in microbiota composition consequent to dimethyl fumarate treatment.
Measured: 6 months of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2017
- Study startFeb 2015
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Multiple Sclerosis Center of Northeastern New York
- Sponsor type
- University, hospital or other
- Collaborators
- Icahn School of Medicine at Mount Sinai, Biogen
- Responsible party
- Sponsor
- Investigators
- Keith R Edwards, M.D., Principal investigator, MS Center of Northeastern NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03092544
- Sponsor's protocol ID
- BG12-002
- Status last verified
- Mar 2018
- First submitted
- 23 Jun 2016
- Last updated
- 22 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kim JY, Shen S, Dietz K, He Y, Howell O, Reynolds R, Casaccia P. HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage. Nat Neurosci. 2010 Feb;13(2):180-9. doi: 10.1038/nn.2471. Epub 2009 Dec 27.
PubMed 20037577Vidaurre OG, Haines JD, Katz Sand I, Adula KP, Huynh JL, McGraw CA, Zhang F, Varghese M, Sotirchos E, Bhargava P, Bandaru VV, Pasinetti G, Zhang W, Inglese M, Calabresi PA, Wu G, Miller AE, Haughey NJ, Lublin FD, Casaccia P. Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics. Brain. 2014 Aug;137(Pt 8):2271-86. doi: 10.1093/brain/awu139. Epub 2014 Jun 3.
PubMed 24893707
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Indirect Mechanism of Neuroprotection of Tecfidera® (Dimethyl Fumarate) in RRMS and Progressive Patients
- ClinicalTrials.gov ID
- NCT03092544
- Acronym / sponsor ID
- BG12-002
- Conditions
- Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Multiple Sclerosis Center of Northeastern New YorkUniversity, hospital or other
- Collaborators
- Icahn School of Medicine at Mount Sinai, Biogen
- Study start
- Feb 2015
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 28 Mar 2017 (actual)
- 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 purposes of this study is to identify types of bacteria that reside in the intestine of healthy individuals and compare them to individuals with Multiple Sclerosis (MS). There has been a lot of research in other autoimmune diseases which has demonstrated the importance of stomach "gut" bacteria because it has an important relationship with the immune system, but this has never been studied in MS patients. In this study investigators aim to show differences in the gut bacteria between healthy individuals and those with MS, to provide a basis for future research studying how diet can affect MS through its effects on the "gut" bacteria.
Additionally, this study will be looking at the effects of dimethyl fumarate on cerebrospinal fluid, plasma and MRI in MS patients taking dimethyl fumarate as compared to those with MS not on dimethyl fumarate or other disease modifying therapy and those who do not have MS (normal controls).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| RRMS on therapy | Active comparator | Drug: dimethyl fumarate18 subjects with a diagnosis of Relapsing Remitting (RRMS) ages 18-55, that are scheduled to begin on dimethyl fumarate |
| SPMS on therapy | Active comparator | Drug: dimethyl fumarate18 subjects with a diagnosis of Secondary Progressive (SPMS) ages 25-65 without clinical or MRI evidence of relapse in two years that are scheduled to begin on dimethyl fumarate |
| SPMS not on therapy | No intervention | –18 subjects with a diagnosis of SPMS ages 25-65 without clinical or MRI evidence of relapse in two years, that are NOT scheduled to begin on dimethyl fumarate |
| Normal Control 1 | No intervention | –10 normal controls (younger cohort, mean age 38) |
| Normal Control 2 | No intervention | –10 normal controls (younger cohort, mean age 58) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Male or female subject, age 18-65 (inclusive) at the time of informed consent, with a confirmed diagnosis of multiple sclerosis and meeting multiple sclerosis patient population as specified in section 4/ study design/multiple sclerosis population of this protocol.
- Subject has the ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Expanded Disability Status Scale (EDSS) score between 0 and 7, inclusive, at screen.
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
Key exclusion criteria (46 listed)
- General and Medical History Exclusions
- A MS relapse, as determined by the investigator, that occurred within 90 days prior to screen or the subject has not stabilized from a previous relapse prior to screen visit.
- Current smoker
- Any contraindication to having a brain MRI (e.g. pacemaker, MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed) or contraindication for administration of gadolinium-contrast agents.
- Clinically significant brain MRI findings other than those related to MS, as judged by the investigator, at screen.
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 |
|---|---|---|
| dimethyl fumarateAlso: Tecfidera,Active drug | Drug | RRMS on therapy, SPMS on therapy |
Primary outcome
Change in plasma samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics
Time frame: change from baseline at 6 months treatment with dimethyl fumarate
Change in cerebrospinal (CSF) samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics
Time frame: change from baseline at 6 months treatment with dimethyl fumarate
change in levels of neurofilament( NFL) in RRMS patients
Time frame: at baseline and after 6 months of therapy
change in levels of ceramide sphyngosine and other lipid species in samples collected from patients before and after therapy in CSF samples in RRMS patients
Time frame: at baseline and 6 months of therapy
changes in microbiota composition consequent to dimethyl fumarate treatment.
Time frame: 6 months of therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
- Background: PubMed 20037577Kim JY, Shen S, Dietz K, He Y, Howell O, Reynolds R, Casaccia P. HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage. Nat Neurosci. 2010 Feb;13(2):180-9. doi: 10.1038/nn.2471. Epub 2009 Dec 27.
- Background: PubMed 24893707Vidaurre OG, Haines JD, Katz Sand I, Adula KP, Huynh JL, McGraw CA, Zhang F, Varghese M, Sotirchos E, Bhargava P, Bandaru VV, Pasinetti G, Zhang W, Inglese M, Calabresi PA, Wu G, Miller AE, Haughey NJ, Lublin FD, Casaccia P. Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics. Brain. 2014 Aug;137(Pt 8):2271-86. doi: 10.1093/brain/awu139. Epub 2014 Jun 3.
- Individual participant dataSharing planned: No
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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.
Keith R Edwards, M.D. principal investigator
MS Center of Northeastern NY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dimethyl fumarate in people with Multiple Sclerosis, run by Multiple Sclerosis Center of Northeastern New York at 1 site in United States.
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 7 inclusion and 46 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: status not confirmed, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Change in plasma samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics (time frame: change from baseline at 6 months treatment with dimethyl fumarate). The study lists 5 primary outcomes in all. 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 NCT03092544, which also lists 2 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 22 Mar 2018.