Multiple SclerosisPhase 2NCT00011375
Rolipram to Treat Multiple Sclerosis
A Phase 2 study testing Rolipram in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will evaluate the safety, tolerability, and effect of the drug Rolipram on multiple sclerosis (MS). It will examine whether Rolipram can dampen the part of the immune response believed to lead to MS and reduce disease activity. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Rolipram
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2001to Apr 2004
- Phase
- Phase 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Stage I:
- Between the ages of 18 and 65 years, inclusive.
- Subjects with clinically definite relapsing-remitting or secondary progressive multiple sclerosis according to pubished criteria.
- EDSS score between 4.0 and 6.5.
- Patients have either failed standard treatment (interferon beta, glatiramer acetate) by clinical measures and/or were not eligible for ay of the standard treatments available or opted not to start or to continue with any of these treatments.
- Stage II:
Show all 14Show fewer
- Same as Stage I with exceptiom that EDSS will be between 1.5 and 6.5.
- Eligibility Criteria For Initiating Therapy:
- Stage I:
- Subjects must have an average of up to 2 Gd-enhancing lesions per month over the 3 month pre-treatment baseline period (i.e. over 4 MRI scans).
- Stage II:
- Subjects must have an average of at least 0.5 Gd-enhancing lesions per month over the 4 month pre-treatment baseline period.
- Stage I \& II:
- Subjects must not have a relapse during 30 days before initiation of treatment. If a relapse occurs during the last 30 days of the pre-treatment baseline period and eligibility MRI criteria are fulfilled, beginning of the treatment (day 1) is delayed for at least so many days that treatment starts not earlier than 30 days after the relapse and not earlier than 60 days in case i.v. corticosteroids had been given. Similarly, the baseline needs to be prolonged if corticosteroid treatments become necessary during these three months.
Who cannot join
- Patients will be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment. If a washout period of previous treatments becomes necessary, these criteria have to be assessed again at the beginning of the MRI baseline period. An additional assessment of the exclusion criteria follows on day 0 of the 6 months treatment phase.
- Medical History: Blood tests exceeding any of the limits defined below will lead to exclusion from the study: ALT (SGPT) or AST (SGOT) is greater than three times the upper limit of normal; total white blood cell count is less than 3,000/mm(3), neutrophils less than 2,000; platelet count of less than 85, 000/mm(3); creatinine greater than 1.5 mg/dl; serology indicating HIV infection or active hepatitis A, B, or C infection; postive pregnancy test or breast-feeding female; nausea/vomiting as a frequent complaint; fasting prolactin levels of greater than 20 micrograms/L; history or signs of immunodeficiency; history of galactorrhea and/or history of prolactin-secreting tumors, history of pituitary tumors and adenomas, history of mammary tumors; clinically relevant arrhythmia or other ECG abnormalities.
- Clinically significant (as determined by the investigator) cardiac, immunological, pulmonary, neurological, renal, and/or other major disease including ECG, echocardiogram, and chest x-ray examinations.
- Patients with mental impairment that would compromise understanding and judging the consent will be excluded from the study and who are thus not able to give informed consent will be excluded fromthe study. Other neurocognitive deficits or physical disabilities are no exclusion criteria.
- Treatment History: If prior treatment was recieved, the subject must have been off treatment for the required period prior to enrollment.
- Miscellaneous: History of alcohol or drug abuse within the 5 years prior to enrollment; female subjects who are not post-menopausal or surgically sterile who are not using an acceptable method of contraception; male subjects not practicing adequate contraception; breastfeeding patients; unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's returing for follow-up visits on schedule; previous participation in this study; and inability to understand/give the informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Safety, Tolerability & Effects of Rolipram on Inflammatory Activity in the Central Nervous System in Multiple Sclerosis. A Phase II, Open Label Crossover Trial Using MRI as an Outcome Measure
This study will evaluate the safety, tolerability, and effect of the drug Rolipram on multiple sclerosis (MS). It will examine whether Rolipram can dampen the part of the immune response believed to lead to MS and reduce disease activity.
Patient with multiple sclerosis who are between the ages of 18 and 65 may be eligible for this study. Candidates will be screened with a complete neurological and medical evaluation. Participants will complete three study phases-baseline, treatment and follow-up, as follows:
Read more
Baseline (3 months) - Approximately four magnetic resonance imaging (MRI) scans will be obtained to assess MS activity. Participants with MS activity above a certain level will continue with the treatment phase.
Treatment (8 months) - Patients will take Rolipram tablets in increasing doses every 2 to 3 days for the first month of this phase until their individual maximum tolerated dose is established. Dosing will continue at that level for the rest of the treatment phase. Dosing is in the morning, midday and evening. Patients will be seen monthly in the clinic for examination and MRI scans.
Follow-up - Participants will have monthly exams and MRIs for 3 months following the treatment phase, after which their participation in the study ends.
Patients' monthly visits during treatment and follow-up include a neurological examination to assess disease status; MRI to assess brain changes; and blood and urine collection to monitor liver, kidney and other functions. In addition, a lumbar puncture (spinal tap) is done during the last month of the baseline phase and one month after treatment ends to study changes in the spinal fluid surrounding the brain and spinal cord, and leukapheresis is done once during the last month of the baseline phase and once during the last month of treatment to collect white blood cells for study. These procedures involve the following:
MRI uses a strong magnetic field and radio waves instead of X-rays to produce images showing structural and chemical changes in tissues. The patient lies on a table in a narrow cylinder (the scanner) containing a magnetic field and images are taken. A contrast agent called gadolinium is injected into a vein during the last set of images to help identify new lesions. Magnetic resonance spectroscopy, which is similar to MRI, is also done once during the baseline phase, at 4 months and at 8 months to measure brain chemicals. For the spinal tap, a local anesthetic is given and a needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle. For leukapheresis, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the red cells, platelets and plasma are returned to the body through a second needle placed in the other arm.
Patients may also have studies to measure levels of Rolipram in the blood. These are done on study days 1 and 29 and at months 2, 4, and 6. For days 1 and 29, a catheter is placed in an arm vein and 4 ml. of blood is drawn immediately before the morning dose and at several intervals from 20 minutes to 6 hours after the dose. For the other tests, a single 4-ml sample is collected before the noon dose.
Read the detailed description
Rolipram is a phosphodiesterase (PDE) type 4 inhibitor that has originally been developed by Schering AG, Berlin, Germany, as an antidepressant, before others and our laboratory documented the immunomodulatory properties of the drug. In the current trial, Rolipram will for the first time be tested as a novel immunomodulatory therapy in multiple sclerosis patients. The protocol involves a stage I for finding the highest individually well-tolerated drug dose, before stage II, and 8 months treatment period with this individually well-tolerated dose, will be conducted. The trial shall document the safety, tolerability an efficacy with respect to inhibition of central nervous inflammation in multiple sclerosis patients. Magnetic resonance imaging and clinical examinations will be used to study the above parameters, and immunological studies that will be conducted in parallel to the trial, will address the mechanism of action of Rolipram in MS.
- Conditions
- Multiple Sclerosis
- Being tested
- Rolipram
- Keywords
- Phosphodiesterase Inhibitor, Immunology, Immunomodulation, Antidepressant, Therapy, Multiple Sclerosis, Immunotherapy
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RolipramDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2001 (estimated)
- Study startFeb 2001
- Study completionApr 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)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 2
- Primary purpose
- Treatment
- Enrolment
- 52 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00011375
- Sponsor's protocol ID
- 010089
- Other IDs
- 01-N-0089
- Status last verified
- Apr 2004
- First submitted
- 16 Feb 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Sommer N, Loschmann PA, Northoff GH, Weller M, Steinbrecher A, Steinbach JP, Lichtenfels R, Meyermann R, Riethmuller A, Fontana A, et al. The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. Nat Med. 1995 Mar;1(3):244-8. doi: 10.1038/nm0395-244.
PubMed 7585041Hasko G, Szabo C, Nemeth ZH, Salzman AL, Vizi ES. Suppression of IL-12 production by phosphodiesterase inhibition in murine endotoxemia is IL-10 independent. Eur J Immunol. 1998 Feb;28(2):468-72. doi: 10.1002/(SICI)1521-4141(199802)28:023.0.CO;2-Z.
PubMed 9521054Pette M, Muraro PA, Pette DF, Dinter H, McFarland HF, Martin R. Differential effects of phosphodiesterase type 4-specific inhibition on human autoreactive myelin-specific T cell clones. J Neuroimmunol. 1999 Aug 3;98(2):147-56. doi: 10.1016/s0165-5728(99)00088-0.
PubMed 10430048
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability & Effects of Rolipram on Inflammatory Activity in the Central Nervous System in Multiple Sclerosis. A Phase II, Open Label Crossover Trial Using MRI as an Outcome Measure
- ClinicalTrials.gov ID
- NCT00011375
- Acronym / sponsor ID
- 010089
- Conditions
- Multiple Sclerosis
- Keywords
- Phosphodiesterase Inhibitor, Immunology, Immunomodulation, Antidepressant, Therapy, Multiple Sclerosis, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Feb 2001
- Study completion
- Apr 2004
- First posted
- 19 Feb 2001 (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.
This study will evaluate the safety, tolerability, and effect of the drug Rolipram on multiple sclerosis (MS). It will examine whether Rolipram can dampen the part of the immune response believed to lead to MS and reduce disease activity.
Patient with multiple sclerosis who are between the ages of 18 and 65 may be eligible for this study. Candidates will be screened with a complete neurological and medical evaluation. Participants will complete three study phases-baseline, treatment and follow-up, as follows:
Baseline (3 months) - Approximately four magnetic resonance imaging (MRI) scans will be obtained to assess MS activity. Participants with MS activity above a certain level will continue with the treatment phase.
Treatment (8 months) - Patients will take Rolipram tablets in increasing doses every 2 to 3 days for the first month of this phase until their individual maximum tolerated dose is established. Dosing will continue at that level for the rest of the treatment phase. Dosing is in the morning, midday and evening. Patients will be seen monthly in the clinic for examination and MRI scans.
Follow-up - Participants will have monthly exams and MRIs for 3 months following the treatment phase, after which their participation in the study ends.
Patients' monthly visits during treatment and follow-up include a neurological examination to assess disease status; MRI to assess brain changes; and blood and urine collection to monitor liver, kidney and other functions. In addition, a lumbar puncture (spinal tap) is done during the last month of the baseline phase and one month after treatment ends to study changes in the spinal fluid surrounding the brain and spinal cord, and leukapheresis is done once during the last month of the baseline phase and once during the last month of treatment to collect white blood cells for study. These procedures involve the following:
MRI uses a strong magnetic field and radio waves instead of X-rays to produce images showing structural and chemical changes in tissues. The patient lies on a table in a narrow cylinder (the scanner) containing a magnetic field and images are taken. A contrast agent called gadolinium is injected into a vein during the last set of images to help identify new lesions. Magnetic resonance spectroscopy, which is similar to MRI, is also done once during the baseline phase, at 4 months and at 8 months to measure brain chemicals. For the spinal tap, a local anesthetic is given and a needle is inserted in the space between the bones (vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle. For leukapheresis, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the red cells, platelets and plasma are returned to the body through a second needle placed in the other arm.
Patients may also have studies to measure levels of Rolipram in the blood. These are done on study days 1 and 29 and at months 2, 4, and 6. For days 1 and 29, a catheter is placed in an arm vein and 4 ml. of blood is drawn immediately before the morning dose and at several intervals from 20 minutes to 6 hours after the dose. For the other tests, a single 4-ml sample is collected before the noon dose.
Detailed description
Rolipram is a phosphodiesterase (PDE) type 4 inhibitor that has originally been developed by Schering AG, Berlin, Germany, as an antidepressant, before others and our laboratory documented the immunomodulatory properties of the drug. In the current trial, Rolipram will for the first time be tested as a novel immunomodulatory therapy in multiple sclerosis patients. The protocol involves a stage I for finding the highest individually well-tolerated drug dose, before stage II, and 8 months treatment period with this individually well-tolerated dose, will be conducted. The trial shall document the safety, tolerability an efficacy with respect to inhibition of central nervous inflammation in multiple sclerosis patients. Magnetic resonance imaging and clinical examinations will be used to study the above parameters, and immunological studies that will be conducted in parallel to the trial, will address the mechanism of action of Rolipram in MS.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Between the ages of 18 and 65 years, inclusive.
- Subjects with clinically definite relapsing-remitting or secondary progressive multiple sclerosis according to pubished criteria.
- EDSS score between 4.0 and 6.5.
- Patients have either failed standard treatment (interferon beta, glatiramer acetate) by clinical measures and/or were not eligible for ay of the standard treatments available or opted not to start or to continue with any of these treatments.
- Same as Stage I with exceptiom that EDSS will be between 1.5 and 6.5.
Key exclusion criteria (6 listed)
- Patients will be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment. If a washout period of previous treatments becomes necessary, these criteria have to be assessed again at the beginning of the MRI baseline period. An additional assessment of the exclusion criteria follows on day 0 of the 6 months treatment phase.
- Medical History: Blood tests exceeding any of the limits defined below will lead to exclusion from the study: ALT (SGPT) or AST (SGOT) is greater than three times the upper limit of normal; total white blood cell count is less than 3,000/mm(3), neutrophils less than 2,000; platelet count of less than 85, 000/mm(3); creatinine greater than 1.5 mg/dl; serology indicating HIV infection or active hepatitis A, B, or C infection; postive pregnancy test or breast-feeding female; nausea/vomiting as a frequent complaint; fasting prolactin levels of greater than 20 micrograms/L; history or signs of immunodeficiency; history of galactorrhea and/or history of prolactin-secreting tumors, history of pituitary tumors and adenomas, history of mammary tumors; clinically relevant arrhythmia or other ECG abnormalities.
- Clinically significant (as determined by the investigator) cardiac, immunological, pulmonary, neurological, renal, and/or other major disease including ECG, echocardiogram, and chest x-ray examinations.
- Patients with mental impairment that would compromise understanding and judging the consent will be excluded from the study and who are thus not able to give informed consent will be excluded fromthe study. Other neurocognitive deficits or physical disabilities are no exclusion criteria.
- Treatment History: If prior treatment was recieved, the subject must have been off treatment for the required period prior to enrollment.
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 |
|---|---|---|
| Rolipram | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7585041Sommer N, Loschmann PA, Northoff GH, Weller M, Steinbrecher A, Steinbach JP, Lichtenfels R, Meyermann R, Riethmuller A, Fontana A, et al. The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. Nat Med. 1995 Mar;1(3):244-8. doi: 10.1038/nm0395-244.
- Background: PubMed 9521054Hasko G, Szabo C, Nemeth ZH, Salzman AL, Vizi ES. Suppression of IL-12 production by phosphodiesterase inhibition in murine endotoxemia is IL-10 independent. Eur J Immunol. 1998 Feb;28(2):468-72. doi: 10.1002/(SICI)1521-4141(199802)28:023.0.CO;2-Z.
- Background: PubMed 10430048Pette M, Muraro PA, Pette DF, Dinter H, McFarland HF, Martin R. Differential effects of phosphodiesterase type 4-specific inhibition on human autoreactive myelin-specific T cell clones. J Neuroimmunol. 1999 Aug 3;98(2):147-56. doi: 10.1016/s0165-5728(99)00088-0.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rolipram in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 14 inclusion and 6 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: finished, as of the sponsor's last update on 4 Mar 2008. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00011375, which also lists 3 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 4 Mar 2008; AzTrials last refreshed its copy on 4 Nov 2026.