Multiple Sclerosis, Relapsing-RemittingPhase 1NCT02423083
Oral Guanabenz for Multiple Sclerosis
A Phase 1 study testing Guanabenz in people with Multiple Sclerosis, Relapsing-Remitting and Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: People with multiple sclerosis (MS) get lesions in their brain and spinal cord. These cause neurological symptoms and sometimes disability. Researchers want to see if a blood pressure drug called guanabenz can repair lesions and help people with MS. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
- What is being tested?
- Guanabenz
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2015to 30 Oct 2017
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- MS as defined by the 2010 Revised McDonald MS Diagnostic Criteria (19)
- Age 18-55, inclusive, at the time of the first screening baseline visit
- EDSS 1.0 to 6, inclusive, at the time of the first screening baseline visit
- Able to provide informed consent
- Willing and able to participate in all aspects of trial design and follow-up
- Undergoing treatment with glatiramer acetate for a period of at least 1 year prior to enrollment in the study
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- For female patients, agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception, including
- birth control pills, injected hormones, and vaginal ring; intrauterine device; barrier methods with spermicide, including diaphragm and condom; or surgical sterilization, including hysterectomy, tubal ligation, and vasectomy) for the duration of the study
- ADDITIONAL INCLUSION CRITERION FOR ACTIVE MS COHORT
- -Development of new T2 hyperintense or contrast enhancing lesions by MRI during the screening phase, but 3 such lesions on any single scan
Who cannot join
- Alternative diagnoses that better explain neurological disability and MRI findings
- Clinically significant medical condition that, in the best judgment of the investigators, may expose the patient to undue risk of harm or prevent the patient from completing the study (examples include, but are not limited to, cerebrovascular disease, substance abuse, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative disorder)
- Undergoing treatment with medications that may interact with guanabenz, including anti-hypertensive agents and/or agents leading to increase in catecholamines (such as tricyclic antidepressants and monoamine oxidase inhibitors)
- Medical contraindication to MRI
- Determination, in the best judgment of the investigators, of the need to treat a prospective participant with steroids for management of MS during the screening period
- Pregnant or breastfeeding woman
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- Abnormal screening/baseline blood tests exceeding any of the limits defined below:
- Serum alanine transaminase or aspartate transaminase levels greater than 3 times the upper limit of normal values
- Total white blood cell count < 3000/mm3
- Platelet count < 85000/mm3
- Serum creatinine level > 2.0 mg/dl and eGFR (estimated glomerular filtration rate) < 60
- ADDITIONAL EXCLUSION CRITERIA FOR STABLE MS COHORT
- Evidence of 1 or more clearly documented MS relapses within the last 1 year
- Development of more than 2 lesions per year relative to an MRI performed at least one year before the first screening MRI (the prior MRI can be an outside MRI)
- Development of new T2 hyperintense or contrast-enhancing lesions by MRI during the screening phase
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase I Study of Oral Guanabenz for Multiple Sclerosis
Background:
- People with multiple sclerosis (MS) get lesions in their brain and spinal cord. These cause neurological symptoms and sometimes disability. Researchers want to see if a blood pressure drug called guanabenz can repair lesions and help people with MS.
Read more
Objective:
- To see if guanabenz is safe and well tolerated in people with MS.
Eligibility:
- People 18 55 years old with MS who have taken glatiramer acetate for the past year.
Design:
- Participants will be screened in a separate protocol. For 2 months, they will be examined and have magnetic resonance imaging (MRI) scans. This will decide if they are in the Stable or Active MS study group.
- The study will last 5 months. There will be up to 11 visits, 5 overnight.
- Visit 1: overnight stay at the clinic:
- Medical history and physical exam.
- Health questionnaire
- Bladder ultrasound scan
- Brain MRI
- Electrocardiogram (EKG) to measure heart electrical activity
- Blood will be drawn through an intravenous (IV) line.
- Participants may have tests of strength, muscle tone, and movement.
- They will get their first dose of the study drug, a tablet taken once a day.
- Participants will take the study drug at home and keep a medicine diary.
- The dose will slowly increase. Each time, participants will stay overnight at the clinic. They will have a physical exam, EKG, MRI, and IV blood draw.
- Visit 6: Participants will have a physical exam, MRI, and blood drawn. They will get a schedule to slowly lower their drug dose and stop taking guanabenz.
- Participants will have 2 final visits. They will have a physical exam, EKG, MRI, and IV blood draw.
Read the detailed description
OBJECTIVE:
This Phase 1 clinical study will aim to determine whether therapeutically adequate dosages of guanabenz are safe and well tolerated in patients with multiple sclerosis (MS). It will further provide pharmacokinetic data important for determination of optimal dosing schedule for possible future Phase 2 study.
STUDY POPULATION:
Six patients, ages between 18-55 inclusive, and diagnosis of definite multiple sclerosis by 2010 Revised McDonald Diagnostic Criteria (Polman et al, 2010) will be enrolled. All patients will have been on treatment with glatiramer acetate, a Food and Drug Administration (FDA) approved disease-modifying therapy, for a minimum of year. Four of the patients will be clinically stable with no clinical relapse in the preceding year and no evidence of active inflammation by MRI during the 2-month screening period; 2 patients will be selected based on evidence of on-going, active inflammation seen by MRI during the screening period.
DESIGN:
In this open-label, single site, dose escalation study, the maximum tolerated dose (MTD) of guanabenz in MS patients will be determined. Patients will be screened for participation under the existing MS natural history study 89-N-0045. Sequential patient enrollment will be spaced at least 6 weeks apart. Five study drug doses will be explored: 4mg, 8mg, 16mg, 32mg and 64mg. Dose escalation will ensue if the preceding dose is tolerated, defined both by patient-reported outcomes and objective clinical and imaging assessments. Patients will be maintained on lower doses (4mg-16mg) for 14 days and on higher doses (32 and 64mg) for 28 days.
OUTCOMES:
The primary outcome is MTD, defined as the maximum dose that produces dose-limiting toxicity (DLT) in at most 2 out of the 6 participants. Secondary outcomes include patient-reported outcomes, objective clinical and imaging assessments at 32mg and 64mg, and pharmacokinetics.
- Being tested
- Guanabenz
- Keywords
- Neuroprotection, Multiple Sclerosis, Clinical Trial, Safety and Tolerability
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GuanabenzDrug
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Not described Receives: Drug: Guanabenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Measured: 3.5 months
Secondary outcomes (1)
Pharmacokinetics of guanabenz in MS patients
Measured: 3.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study start21 Apr 2015
- Primary completion30 Oct 2017
- Study completion30 Oct 2017
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, Relapsing-RemittingStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irene CM Cortese, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423083
- Sponsor's protocol ID
- 150117
- Other IDs
- 15-N-0117
- Status last verified
- 30 Oct 2017
- First submitted
- 21 Apr 2015
- Last updated
- 12 Dec 2019
- Results posted
- No
Publications
Lin W, Popko B. Endoplasmic reticulum stress in disorders of myelinating cells. Nat Neurosci. 2009 Apr;12(4):379-85. doi: 10.1038/nn.2273. Epub 2009 Mar 15.
PubMed 19287390Lin W, Kunkler PE, Harding HP, Ron D, Kraig RP, Popko B. Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am J Pathol. 2008 Nov;173(5):1508-17. doi: 10.2353/ajpath.2008.080449. Epub 2008 Sep 25.
PubMed 18818381Lin W, Lin Y, Li J, Fenstermaker AG, Way SW, Clayton B, Jamison S, Harding HP, Ron D, Popko B. Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J Neurosci. 2013 Apr 3;33(14):5980-91. doi: 10.1523/JNEUROSCI.1636-12.2013.
PubMed 23554479Clayton BLL, Popko B. Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia. Brain Res. 2016 Oct 1;1648(Pt B):594-602. doi: 10.1016/j.brainres.2016.03.046. Epub 2016 Apr 4.
PubMed 27055915
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Oral Guanabenz for Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT02423083
- Acronym / sponsor ID
- 150117
- Keywords
- Neuroprotection, Multiple Sclerosis, Clinical Trial, Safety and Tolerability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 21 Apr 2015
- Primary completion
- 30 Oct 2017 (actual)
- Study completion
- 30 Oct 2017 (actual)
- First posted
- 22 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.
Background:
- People with multiple sclerosis (MS) get lesions in their brain and spinal cord. These cause neurological symptoms and sometimes disability. Researchers want to see if a blood pressure drug called guanabenz can repair lesions and help people with MS.
Objective:
- To see if guanabenz is safe and well tolerated in people with MS.
Eligibility:
- People 18 55 years old with MS who have taken glatiramer acetate for the past year.
Design:
- Participants will be screened in a separate protocol. For 2 months, they will be examined and have magnetic resonance imaging (MRI) scans. This will decide if they are in the Stable or Active MS study group.
- The study will last 5 months. There will be up to 11 visits, 5 overnight.
- Visit 1: overnight stay at the clinic:
- Medical history and physical exam.
- Health questionnaire
- Bladder ultrasound scan
- Brain MRI
- Electrocardiogram (EKG) to measure heart electrical activity
- Blood will be drawn through an intravenous (IV) line.
- Participants may have tests of strength, muscle tone, and movement.
- They will get their first dose of the study drug, a tablet taken once a day.
- Participants will take the study drug at home and keep a medicine diary.
- The dose will slowly increase. Each time, participants will stay overnight at the clinic. They will have a physical exam, EKG, MRI, and IV blood draw.
- Visit 6: Participants will have a physical exam, MRI, and blood drawn. They will get a schedule to slowly lower their drug dose and stop taking guanabenz.
- Participants will have 2 final visits. They will have a physical exam, EKG, MRI, and IV blood draw.
Detailed description
OBJECTIVE:
This Phase 1 clinical study will aim to determine whether therapeutically adequate dosages of guanabenz are safe and well tolerated in patients with multiple sclerosis (MS). It will further provide pharmacokinetic data important for determination of optimal dosing schedule for possible future Phase 2 study.
STUDY POPULATION:
Six patients, ages between 18-55 inclusive, and diagnosis of definite multiple sclerosis by 2010 Revised McDonald Diagnostic Criteria (Polman et al, 2010) will be enrolled. All patients will have been on treatment with glatiramer acetate, a Food and Drug Administration (FDA) approved disease-modifying therapy, for a minimum of year. Four of the patients will be clinically stable with no clinical relapse in the preceding year and no evidence of active inflammation by MRI during the 2-month screening period; 2 patients will be selected based on evidence of on-going, active inflammation seen by MRI during the screening period.
DESIGN:
In this open-label, single site, dose escalation study, the maximum tolerated dose (MTD) of guanabenz in MS patients will be determined. Patients will be screened for participation under the existing MS natural history study 89-N-0045. Sequential patient enrollment will be spaced at least 6 weeks apart. Five study drug doses will be explored: 4mg, 8mg, 16mg, 32mg and 64mg. Dose escalation will ensue if the preceding dose is tolerated, defined both by patient-reported outcomes and objective clinical and imaging assessments. Patients will be maintained on lower doses (4mg-16mg) for 14 days and on higher doses (32 and 64mg) for 28 days.
OUTCOMES:
The primary outcome is MTD, defined as the maximum dose that produces dose-limiting toxicity (DLT) in at most 2 out of the 6 participants. Secondary outcomes include patient-reported outcomes, objective clinical and imaging assessments at 32mg and 64mg, and pharmacokinetics.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Guanabenz |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- MS as defined by the 2010 Revised McDonald MS Diagnostic Criteria (19)
- Age 18-55, inclusive, at the time of the first screening baseline visit
- EDSS 1.0 to 6, inclusive, at the time of the first screening baseline visit
- Able to provide informed consent
- Willing and able to participate in all aspects of trial design and follow-up
Key exclusion criteria (15 listed)
- Alternative diagnoses that better explain neurological disability and MRI findings
- Clinically significant medical condition that, in the best judgment of the investigators, may expose the patient to undue risk of harm or prevent the patient from completing the study (examples include, but are not limited to, cerebrovascular disease, substance abuse, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative disorder)
- Undergoing treatment with medications that may interact with guanabenz, including anti-hypertensive agents and/or agents leading to increase in catecholamines (such as tricyclic antidepressants and monoamine oxidase inhibitors)
- Medical contraindication to MRI
- Determination, in the best judgment of the investigators, of the need to treat a prospective participant with steroids for management of MS during the screening period
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 |
|---|---|---|
| Guanabenz | Drug | Treatment arm |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: 3.5 months
1 secondary outcome
Pharmacokinetics of guanabenz in MS patients
Time frame: 3.5 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Background: PubMed 19287390Lin W, Popko B. Endoplasmic reticulum stress in disorders of myelinating cells. Nat Neurosci. 2009 Apr;12(4):379-85. doi: 10.1038/nn.2273. Epub 2009 Mar 15.
- Background: PubMed 18818381Lin W, Kunkler PE, Harding HP, Ron D, Kraig RP, Popko B. Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am J Pathol. 2008 Nov;173(5):1508-17. doi: 10.2353/ajpath.2008.080449. Epub 2008 Sep 25.
- Background: PubMed 23554479Lin W, Lin Y, Li J, Fenstermaker AG, Way SW, Clayton B, Jamison S, Harding HP, Ron D, Popko B. Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J Neurosci. 2013 Apr 3;33(14):5980-91. doi: 10.1523/JNEUROSCI.1636-12.2013.
- Derived from this study: PubMed 27055915Clayton BLL, Popko B. Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia. Brain Res. 2016 Oct 1;1648(Pt B):594-602. doi: 10.1016/j.brainres.2016.03.046. Epub 2016 Apr 4.
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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.
Irene CM Cortese, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Guanabenz in people with Multiple Sclerosis, Relapsing-Remitting and 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 10 inclusion and 15 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 12 Dec 2019. 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 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 stopped early. 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?
Maximum tolerated dose (MTD) (time frame: 3.5 months). 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 NCT02423083, 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 12 Dec 2019; AzTrials last refreshed its copy on 28 Oct 2026.