Multiple SclerosisPhase 2perfuseMSNCT02466074
Augmenting Cerebral Blood Flow to Treat Established Multiple Sclerosis
A Phase 2 study testing Acetazolamide in people with Multiple Sclerosis, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
This study will evaluate how improved cerebral blood flow affects the way in which newly formed MS lesions evolve and whether tissue repair is improved. Patients with multiple sclerosis (MS) will be treated with acetazolamide in daily divided doses and obtain MRI to determine how much and in which regions of the brain… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Aug 2016to 7 Feb 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of relapsing forms of multiple sclerosis using revised McDonald criteria
- Stable on any FDA-approved disease-modifying therapy. The term "stable" implies that the subject has not had change in therapy for any reason for the 6 months prior to study entry.
- Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive
- Understood and signed written informed consent, obtained prior to the study subject undergoing any study related procedure, including screening tests.
Who cannot join
- Known hypersensitivity to sulfonamides or derivatives
- Known history of renal or hepatic disease, cerebrovascular disease including stroke, transient ischemic attack, myocardial infarction, angina or congestive heart failure.
- Evidence to suggest hyponatremia or hypokalemia, marked kidney dysfunction defined as creatinine greater than 2.0 mg/dL or liver disease dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three-fold upper limit of normal (ULN).
- Evidence to suggest suprarenal gland failure.
- Evidence of hyperchloremic acidosis.
- Initiation of new immunosuppressant treatment after the subject becomes protocol-eligible (except for corticosteroids) or enrollment in a concurrent trial.
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- Prior treatment with mitoxantrone, natalizumab, methotrexate, cladribine cyclophosphamide or other change in disease modifying therapy (DMT) within 6 months of initiation of study.
- Subjects with any history of cytopenia.
- History of pulmonary obstruction or emphysema.
- Active hepatitis B or hepatitis C infection or evidence of cirrhosis.
- Human immunodeficiency virus (HIV) positivity.
- Uncontrolled diabetes mellitus defined as HbA1c>8% and/or requiring intensive management.
- Uncontrolled viral, fungal, or bacterial infection (excluding asymptomatic bacteriuria).
- Any condition that, in the opinion of the investigators, would jeopardize the ability of the subject to tolerate treatment with ACZ.
- Prior history of malignancy.
- Positive pregnancy test or inability or unwillingness to use effective means of birth control. Effective birth control defines as:
- Refraining from all acts of vaginal intercourse (abstinence)
- Consistent use of birth control pills
- Tubal sterilization or male partner who has undergone vasectomy
- Placement of an intrauterine device (IUD)
- Use, with every act of intercourse, of a diaphragm with contraceptive jelly and/or condoms with contraceptive foam
- Presence of metallic objects implanted in the body that would preclude the ability of the subject to safely have MRI exams.
- Psychiatric illness, mental deficiency, or cognitive dysfunction making compliance with treatment of informed consent impossible.
Trial locations and contacts
1 site in 1 country.
About this study
This study will evaluate how improved cerebral blood flow affects the way in which newly formed MS lesions evolve and whether tissue repair is improved. Patients with multiple sclerosis (MS) will be treated with acetazolamide in daily divided doses and obtain MRI to determine how much and in which regions of the brain cerebral perfusion improves as well as the extent to which tissue integrity is improved in these areas.
Read the detailed description
Cerebral perfusion is altered in many disease states, including MS. Altered perfusion has been seen in patients with all multiple sclerosis (MS) phenotypes and is well established as occurring early in relapsing-remitting disease.
Previous research in our laboratory has shown that reduced cerebral perfusion in MS patients is a precursor to the formation of chronic lesions. In addition, studies have suggested that "virtual hypoxia", resultant from the combination of diminished cerebral perfusion and increased energy demand, contributes to tissue damage that strongly correlates with clinical disability in persons with MS. Our preliminary studies have already shown short-term increases in global and regional cerebral perfusion in MS patients after therapy with acetazolamide (ACZ).
The central hypothesis is that if cerebral perfusion is important in tissue injury, then MS lesions within hypoperfused areas are more likely to develop permanent tissue damage, and medications that improve cerebral perfusion might beneficially alter the evolution of MS plaques, enhance remyelination and repair and diminish clinical disability progression.
Sixty MS patients will be enrolled in this single-center exploratory RCT. Half of the patients will be randomly assigned to get ACZ treatment in phase 1 consisting of 24 weeks on ACZ, followed by another 24 weeks on ACZ during phase 2. The other half of the patients will be assigned to placebo for 24 weeks in phase 1 and then switched to ACZ and followed for 24 weeks in phase 2. This study will utilize various imaging techniques to determine the degree to which cerebral blood flow is improved in MS subjects after administration of ACZ.
- Conditions
- Multiple Sclerosis
- Being tested
- Acetazolamide, Placebo
- Keywords
- Acetazolamide, Lesions, Neurodegeneration, Repair
- Medical subject headings
- Multiple Sclerosis, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Also called Diamox
see arm description
PlaceboDrug
Placebo arm
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Experimental | Acetazolamide in oral daily divided dose administered for 6 consecutive months Receives: Drug: Acetazolamide |
| Placebo | Placebo comparator | Placebo in oral daily divided dose administered for 6 consecutive months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Global Cerebral Blood Flow
Percent change in global cerebral blood flow (CBF) after 24 weeks relative to pre-treatment baseline. Global CBF is determined using magnetic resonance imaging (MRI) methods.
The data reported indicate the extent of change in global CBF--the higher the percent change, the greater the increase in global CBF and the better the outcome.
Measured: baseline, 24 weeks
Secondary outcomes (2)
Percent Change in Tissue Integrity in White Matter (Mean Diffusivity)
The data reported indicate the extent of change in white matter integrity as determined using the diffusion tensor imaging-magnetic resonance imaging (DTI-MRI) measure of mean diffusivity. A positive percent change value indicates an increase in mean diffusivity between baseline and 24 weeks, and a higher mean diffusivity value indicates a breakdown in white matter integrity, so the greater the percent change, the greater the breakdown of white matter integrity and the worse the outcome.
Measured: baseline, 24 weeks
Percent Change in Tissue Integrity in White Matter (Fractional Anisotropy)
The data reported indicate the extent of change in white matter integrity as determined using the diffusion tensor imaging-magnetic resonance imaging (DTI-MRI) measure of fractional anisotropy. A negative percent change value indicates a decrease in fractional anisotropy between baseline and 24 weeks, and a lower fractional anisotropy value indicates a breakdown in white matter integrity, so the lower (and more negative) the percent change, the greater the breakdown of white matter integrity and the worse the outcome.
Measured: baseline, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2015 (estimated)
- Study start17 Aug 2016
- Primary completion7 Feb 2022
- Study completion7 Feb 2022
Why it stopped: Inadequate recruitment; termination of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two phase design: phase 1, patients randomized to ACZ or placebo and followed for 24 weeks; phase 2, patients that received placebo in phase 1 switch to ACZ (delayed-start group) and patients that received ACZ in phase 1 continue on ACZ (ACZ-ACZ group)
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John A. Lincoln, The University of Texas Health Science Center, Houston
- Investigators
- John Lincoln, MD, PhD, Principal investigator, UTHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02466074
- Sponsor's protocol ID
- HSC-MS-14-0450
- Acronym
- perfuseMS
- Status last verified
- Mar 2023
- First submitted
- 3 Jun 2015
- Last updated
- 27 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Augmenting Cerebral Blood Flow to Treat Established Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT02466074
- Acronym / sponsor ID
- perfuseMS / HSC-MS-14-0450
- Conditions
- Multiple Sclerosis
- Keywords
- Acetazolamide, Lesions, Neurodegeneration, Repair
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate recruitment; termination of funding
- Enrolment
- 5 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- 17 Aug 2016 (actual)
- Primary completion
- 7 Feb 2022 (actual)
- Study completion
- 7 Feb 2022 (actual)
- First posted
- 9 Jun 2015 (estimated)
- Results
- Posted 1 Mar 2023
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 how improved cerebral blood flow affects the way in which newly formed MS lesions evolve and whether tissue repair is improved. Patients with multiple sclerosis (MS) will be treated with acetazolamide in daily divided doses and obtain MRI to determine how much and in which regions of the brain cerebral perfusion improves as well as the extent to which tissue integrity is improved in these areas.
Detailed description
Cerebral perfusion is altered in many disease states, including MS. Altered perfusion has been seen in patients with all multiple sclerosis (MS) phenotypes and is well established as occurring early in relapsing-remitting disease.
Previous research in our laboratory has shown that reduced cerebral perfusion in MS patients is a precursor to the formation of chronic lesions. In addition, studies have suggested that "virtual hypoxia", resultant from the combination of diminished cerebral perfusion and increased energy demand, contributes to tissue damage that strongly correlates with clinical disability in persons with MS. Our preliminary studies have already shown short-term increases in global and regional cerebral perfusion in MS patients after therapy with acetazolamide (ACZ).
The central hypothesis is that if cerebral perfusion is important in tissue injury, then MS lesions within hypoperfused areas are more likely to develop permanent tissue damage, and medications that improve cerebral perfusion might beneficially alter the evolution of MS plaques, enhance remyelination and repair and diminish clinical disability progression.
Sixty MS patients will be enrolled in this single-center exploratory RCT. Half of the patients will be randomly assigned to get ACZ treatment in phase 1 consisting of 24 weeks on ACZ, followed by another 24 weeks on ACZ during phase 2. The other half of the patients will be assigned to placebo for 24 weeks in phase 1 and then switched to ACZ and followed for 24 weeks in phase 2. This study will utilize various imaging techniques to determine the degree to which cerebral blood flow is improved in MS subjects after administration of ACZ.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two phase design: phase 1, patients randomized to ACZ or placebo and followed for 24 weeks; phase 2, patients that received placebo in phase 1 switch to ACZ (delayed-start group) and patients that received ACZ in phase 1 continue on ACZ (ACZ-ACZ group)
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: AcetazolamideAcetazolamide in oral daily divided dose administered for 6 consecutive months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo in oral daily divided dose administered for 6 consecutive months |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Diagnosis of relapsing forms of multiple sclerosis using revised McDonald criteria
- Stable on any FDA-approved disease-modifying therapy. The term "stable" implies that the subject has not had change in therapy for any reason for the 6 months prior to study entry.
- Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive
- Understood and signed written informed consent, obtained prior to the study subject undergoing any study related procedure, including screening tests.
Key exclusion criteria (23 listed)
- Known hypersensitivity to sulfonamides or derivatives
- Known history of renal or hepatic disease, cerebrovascular disease including stroke, transient ischemic attack, myocardial infarction, angina or congestive heart failure.
- Evidence to suggest hyponatremia or hypokalemia, marked kidney dysfunction defined as creatinine greater than 2.0 mg/dL or liver disease dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than three-fold upper limit of normal (ULN).
- Evidence to suggest suprarenal gland failure.
- Evidence of hyperchloremic acidosis.
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 |
|---|---|---|
| AcetazolamideAlso: Diamoxsee arm description | Drug | Acetazolamide |
| PlaceboPlacebo arm | Drug | Placebo |
Primary outcome
Percent Change in Global Cerebral Blood Flow
Time frame: baseline, 24 weeks
Percent change in global cerebral blood flow (CBF) after 24 weeks relative to pre-treatment baseline. Global CBF is determined using magnetic resonance imaging (MRI) methods. The data reported indicate the extent of change in global CBF--the higher the percent change, the greater the increase in global CBF and the better the outcome.
2 secondary outcomes
Percent Change in Tissue Integrity in White Matter (Mean Diffusivity)
Time frame: baseline, 24 weeks
Percent Change in Tissue Integrity in White Matter (Fractional Anisotropy)
Time frame: baseline, 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
John Lincoln, MD, PhD principal investigator
UTHealth
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 Acetazolamide in people with Multiple Sclerosis, run by The University of Texas Health Science Center, Houston 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 4 inclusion and 23 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 27 Apr 2023. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 1 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change in Global Cerebral Blood Flow (time frame: baseline, 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Apr 2023.