Multiple Sclerosis (MS) - Relapsing-remittingPhase 1/2NCT00095329
Treating Multiple Sclerosis With Sirolimus, an Immune System Suppressor
A Phase 1/2 study testing sirolimus in people with Multiple Sclerosis (MS) - Relapsing-remitting, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety and tolerability of the drug sirolimus in patients with multiple sclerosis (MS) who have failed other treatments. Read more about this study
- Who is it for?
- Ages 18 to 58 years
- Conditions the study is for
- Multiple Sclerosis (MS) - Relapsing-remitting
- What is being tested?
- sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- May 2003to Mar 2005
- Phase
- Phase 1/2
- 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 58 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Relapsing-remitting MS
- Evidence of demyelination on magnetic resonance imaging (MRI) scan
- Expanded Disability Status Scale (EDSS) score between 0 and 6
- Nonresponsive to beta-interferon or Glatiramer acetate therapy
- Discontinuation of beta-interferon or Glatiramer acetate therapy within 1 month prior to study entry
- Willing to use acceptable methods of contraception
Who cannot join
- Primary progressive MS
- Prior treatment with immunosuppressants
- Steroid therapy within 1 month prior to study entry
- Evidence of active infection or cancer
- Heart or hematologic dysfunction
- High levels of lipids in the blood
Show all 19Show fewer
- Use of lipid-lowering agents
- History of cirrhosis or liver disease requiring treatment
- History of hepatitis B or C
- Active cytomegalovirus infection
- Kidney disease requiring treatment
- Active lung disease
- Diabetes
- Hyperthyroidism
- HIV infection
- Tuberculosis
- History of alcohol or drug abuse within 6 months prior to study entry
- Claustrophobia or inability to undergo MRI
- Pregnancy or breast-feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
Boston, Massachusetts, 02115
About this study
Official title: A Phase I/II, Open-Label Pilot Trial to Evaluate the Safety of Rapamune (Sirolimus) in Patients With Multiple Sclerosis
The purpose of this study is to determine the safety and tolerability of the drug sirolimus in patients with multiple sclerosis (MS) who have failed other treatments.
Read the detailed description
MS is a chronic autoimmune disease of the central nervous system in which myelin, the protein sheath that protects nerve cells, is degraded by T cells and macrophages, leading to an eventual loss of neurologic function. MS can be classified as either relapsing-remitting, in which patients experience worsening in symptoms followed by partial or complete recovery of function; or progressive, in which patients have a gradual increase in symptoms, with or without relapses. Standard treatments used to treat relapsing-remitting MS are only modestly effective and may be associated with significant toxicity. There is a need to develop therapies with lower toxicities that can be administered early during the course of disease and have the potential to stop disease progression altogether. Sirolimus has been demonstrated to provide potent immunosuppression in recent clinical trials involving kidney transplantation, and may help people with autoimmune diseases like MS. This study will determine the benefit of sirolimus in MS patients.
Blood and urine collection will occur at screening. Participants will take daily doses of sirolimus for 6 months. There will be nine study visits; they will occur at Days 14, 28, 42, 56, 90, 120, 150, 180, and 225. Medication adverse events, concomitant medications, and vital signs will be recorded at Visits 1 through 8. At all visits, patient compliance to the sirolimus regimen will be measured, and blood and urine collection will occur. Physical and neurological exams, magnetic resonance imaging (MRI) brain scans, MS status tests, and a chest x-ray will be conducted at selected times throughout the study.
- Being tested
- sirolimus
- Keywords
- relapsing-remitting MS, nonresponsive to standard of care MS, sirolimus
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusBiological
| Study group | Role | What they receive |
|---|---|---|
| sirolimus | Experimental | Not described Receives: Biological: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of sirolimus, including number of lesions detected by brain MRI
Tolerability of sirolimus
Mean number of new and overall total number of gadolinium-enhancing lesions reported on sequential brain MRIs
Secondary outcomes (2)
Efficacy, as measured by change in the mean number of new and overall total number of gadolinium-enhancing lesions on pre-treatment brain MRIs, compared to post-treatment
Effect of sirolimus therapy on the immune function of patients with relapsing-remitting multiple sclerosis (RRMS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2004 (estimated)
- Study startMay 2003
- Primary completionMar 2005
- Study completionMar 2005
Why it stopped: Due to slow recruitment.
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 Multiple Sclerosis (MS) - Relapsing-remittingStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence
- Responsible party
- Sponsor
- Investigators
- Samia J. Khoury, MD, Principal investigator, Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00095329
- Sponsor's protocol ID
- DAIT AMS02
- Status last verified
- Sep 2016
- First submitted
- 2 Nov 2004
- Last updated
- 22 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Meier DS, Weiner HL, Khoury SJ, Guttmann CR. Magnetic resonance imaging surrogates of multiple sclerosis pathology and their relationship to central nervous system atrophy. J Neuroimaging. 2004 Jul;14(3 Suppl):46S-53S. doi: 10.1177/1051228404266268.
PubMed 15228759Gonsette RE. New immunosuppressants with potential implication in multiple sclerosis. J Neurol Sci. 2004 Aug 15;223(1):87-93. doi: 10.1016/j.jns.2004.04.025.
PubMed 15261567Lucchinetti C, Bruck W. The pathology of primary progressive multiple sclerosis. Mult Scler. 2004 Jun;10 Suppl 1:S23-30. doi: 10.1191/1352458504ms1027oa.
PubMed 15218806Kovarik JM, Burtin P. Immunosuppressants in advanced clinical development for organ transplantation and selected autoimmune diseases. Expert Opin Emerg Drugs. 2003 May;8(1):47-62. doi: 10.1517/14728214.8.1.47.
PubMed 14610911
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Open-Label Pilot Trial to Evaluate the Safety of Rapamune (Sirolimus) in Patients With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00095329
- Acronym / sponsor ID
- DAIT AMS02
- Keywords
- relapsing-remitting MS, nonresponsive to standard of care MS, sirolimus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to slow recruitment.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence
- Study start
- May 2003
- Primary completion
- Mar 2005 (actual)
- Study completion
- Mar 2005 (actual)
- First posted
- 3 Nov 2004 (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 determine the safety and tolerability of the drug sirolimus in patients with multiple sclerosis (MS) who have failed other treatments.
Detailed description
MS is a chronic autoimmune disease of the central nervous system in which myelin, the protein sheath that protects nerve cells, is degraded by T cells and macrophages, leading to an eventual loss of neurologic function. MS can be classified as either relapsing-remitting, in which patients experience worsening in symptoms followed by partial or complete recovery of function; or progressive, in which patients have a gradual increase in symptoms, with or without relapses. Standard treatments used to treat relapsing-remitting MS are only modestly effective and may be associated with significant toxicity. There is a need to develop therapies with lower toxicities that can be administered early during the course of disease and have the potential to stop disease progression altogether. Sirolimus has been demonstrated to provide potent immunosuppression in recent clinical trials involving kidney transplantation, and may help people with autoimmune diseases like MS. This study will determine the benefit of sirolimus in MS patients.
Blood and urine collection will occur at screening. Participants will take daily doses of sirolimus for 6 months. There will be nine study visits; they will occur at Days 14, 28, 42, 56, 90, 120, 150, 180, and 225. Medication adverse events, concomitant medications, and vital signs will be recorded at Visits 1 through 8. At all visits, patient compliance to the sirolimus regimen will be measured, and blood and urine collection will occur. Physical and neurological exams, magnetic resonance imaging (MRI) brain scans, MS status tests, and a chest x-ray will be conducted at selected times throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sirolimus | Experimental | Biological: sirolimus |
Who may qualify
- Ages
- 18 to 58 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Relapsing-remitting MS
- Evidence of demyelination on magnetic resonance imaging (MRI) scan
- Expanded Disability Status Scale (EDSS) score between 0 and 6
- Nonresponsive to beta-interferon or Glatiramer acetate therapy
- Discontinuation of beta-interferon or Glatiramer acetate therapy within 1 month prior to study entry
Key exclusion criteria (19 listed)
- Primary progressive MS
- Prior treatment with immunosuppressants
- Steroid therapy within 1 month prior to study entry
- Evidence of active infection or cancer
- Heart or hematologic dysfunction
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 |
|---|---|---|
| sirolimus | Biological | sirolimus |
Primary outcome
Safety of sirolimus, including number of lesions detected by brain MRI
Tolerability of sirolimus
Mean number of new and overall total number of gadolinium-enhancing lesions reported on sequential brain MRIs
2 secondary outcomes
Efficacy, as measured by change in the mean number of new and overall total number of gadolinium-enhancing lesions on pre-treatment brain MRIs, compared to post-treatment
Effect of sirolimus therapy on the immune function of patients with relapsing-remitting multiple sclerosis (RRMS)
Results and safety
The study was stopped early (reason given: Due to slow recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2016.
- Background: PubMed 15228759Meier DS, Weiner HL, Khoury SJ, Guttmann CR. Magnetic resonance imaging surrogates of multiple sclerosis pathology and their relationship to central nervous system atrophy. J Neuroimaging. 2004 Jul;14(3 Suppl):46S-53S. doi: 10.1177/1051228404266268.
- Background: PubMed 15261567Gonsette RE. New immunosuppressants with potential implication in multiple sclerosis. J Neurol Sci. 2004 Aug 15;223(1):87-93. doi: 10.1016/j.jns.2004.04.025.
- Background: PubMed 15218806Lucchinetti C, Bruck W. The pathology of primary progressive multiple sclerosis. Mult Scler. 2004 Jun;10 Suppl 1:S23-30. doi: 10.1191/1352458504ms1027oa.
- Background: PubMed 14610911Kovarik JM, Burtin P. Immunosuppressants in advanced clinical development for organ transplantation and selected autoimmune diseases. Expert Opin Emerg Drugs. 2003 May;8(1):47-62. doi: 10.1517/14728214.8.1.47.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
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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.
Samia J. Khoury, MD principal investigator
Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing sirolimus in people with Multiple Sclerosis (MS) - Relapsing-remitting, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 6 inclusion and 19 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: stopped early, as of the sponsor's last update on 22 Sep 2016. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 stopped early (reason given: Due to slow recruitment.). 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?
Safety of sirolimus, including number of lesions detected by brain MRI. The study lists 3 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 NCT00095329, 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 22 Sep 2016.