Lisinopril in Multiple Sclerosis

Protocol Complete—Available for Comment

 

 

Why lisinopril in multiple sclerosis (MS)?

  • Multiple sclerosis is a disease of the immune system which acts against patients' own nervous system cells.  Available therapies modulate the immune system

  • Treatments are modestly effective, but all have undesired side effects, some serious

  • Lisinopril (an ACE inhibitor) is a drug that has been used in millions of patients worldwide for years as a safe and effective treatment for hypertension

  • Lisinopril has been tested in well-established animal models of MS. Results provide compelling evidence that ACE inhibitors modulate immune response

  • TLS is testing lisinopril as an adjunctive therapy in patients with MS; if clinical studies confirm its utility, as an inexpensive solution it might provide a real alternative for thousands suffering with MS

 Please take part in designing an innovative clinical study of lisinopril in MS.

Start Protocol Builder Now

An Opportunity for Publication

All participants will be able to review and comment on drafts of the protocol as they are produced, and they will be mailed a TLS Development Team membership certificate to show their support for open innovation.

Participating in the Protocol Builder also enters you into a friendly competition among the research community. When we identify the researchers who have provided the best input for a certain section of the Protocol Builder, we will name them the winners of the section. This can be up to three participants per section.

By winning a section, researchers will enter into a discussion with the TLS study team on how to draft the best protocol. When this protocol is published, the top researchers will have co-authorship rights and an ongoing say into the design and implementation of the trial.

Protocol Builder Results

Rationale

We've reached a unanimous decision. Here are excerpts from users' reasoning:

  • It makes sense and the animal model has previously been proven predictive of clinical efficacy in this indication.
  • The critical activity of ACE on macrophages is also substantial for MS.
  • ​Perhaps, since ACE inhibitors dilate blood vessels, the mechanism is similar to that proposed by Dr. Zamboni. If MS is associated with chronic cerebrospinal venous insufficiency (still to be proven), it is possible that if ACE inhibitors dilate jugular and azygous veins, cerebrospinal venous drainage might improve resulting in improvement in symptoms (the mechanism for this is unknown, Dr. Zamboni postulated a link to iron deposition.
We have reached a broad consensus on our rational. Do you have anything to add?

Please click the rationale heading above to view the rationale. Then feel free to comment on it in the forum.

All respondants have answered that they agree. We're encouraged with these findings, but we'd like you to give us more detail in the forum. Was there one point in particular that you agreed with? Would you strike any aspects from the rationale?

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Population

Researcher Population Results

Question No Yes Total Responses
Relapsing Remitting 2 11 13
Primary Progressive 3 5 8
Secondary Progressive  2 4 6
Progressive Relapsing 4 3 7
The crowd has chosen relapsing remitting MS. Do you agree? Let us know in the forum.

Patients were asked to provide demographic information, which included their diagnosis. This data can be found by clicking to view the Protocol Builder results above.

Relapsing remitting MS has been crowd-selected as our study population. Please view the protocol for more detailed information.

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Dose

20 to 40mg was favored slightly by researchers. Please see the full results to find the written-in responses, and feel free to comment in the forum.

Patient respondents were asked if they ever needed a higher or lower dose of a medication, and most answered that they did not need an altered dose of any certain medication. Is this in line with your experience? Let us know in the forum.

We received a lot of researcher feedback on this topic. Make sure to check the full results at the top of the page.

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Primary Endpoint

We have decided to use the Multiple Sclerosis Functional Composite (MSFC) as our primary endpoint. Please see the protocol for further information.

The Patient Protocol Builder included questions on specific endpoints as well as requests for symptom information. Please read through the results, and feel free to comment in the forum.

Do you have any further comments on the MSFC? Let us know in the forum.

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Secondary Endpoints

Researcher Secondary Endpoint Results

Question Must Have Nice to Have Not Needed Total
Assessment of ambulatory & functional capability 10 3 0 13
Assessment of disease progression 8 5 0 13
Assessment of quality of life / daily living 3 6 2 11
Assessment of fatigue 6 3 3 12
Other 3 1 1 5
We received many written-in suggestions from both researchers and patients. Please read the full results to see the spectrum of responses.

Patients were asked to provide telemedicine opportunities, and we received an array of answers. Please discuss the telemedicine potential in the forum.

We received a lot of varying opinions. Please continue the discussion in the forum.

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Regulatory

We've reached a unanimous decision. Here are excerpts from users' reasoning:

  • It is a generic marketed compound and you are studying an approaved dose and dose form
  • Lisinopril is an approved drug for multiple indications, so OK to cross-reference the tox and CMC package already on file.
  • ​It may require access to the original dossier, which should be discussed with the FDA.
  • ​If my review of the patent situation is correct (orange book patents expired), a 505b2 is permitted for a new indication if the patent is expired and the formulation is not changing.
We reached unanimous consensus. Are we correct in this belief?

Let us know your thoughts on drug regulation in the forum by cicking the comments button below.

Is there a nuance to your opinion that you were not able to express? Let us know in the forum.

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Genotyping

Genotyping Results

Question Yes No Total
Should genotyping be used in the study? 11 3 14
Should patients be randomized based on genotyping results? 5 6 11

 

Genotyping Test Results
Test Response Percentage
OAS1 3 50%
rs6897932 / IL-7 2 33%
Other 4 67%
We found general support for genotyping, but researchers also wrote in a few qualifications. You can find their responses in the results link above.

To see the types of genotyping available for use, click the genotyping heading above.

The majority is in favor of genotyping.

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Statistics

We have no data to display yet.

Please check back for updates.

We are still actively recruiting statistician input. Please use the links above to forward this page to relevant contacts.

Please contribute to the statistical discussion in the forum.

We have yet to reach a consensus. Please post your ideas in the forum, and feel free to recruit a colleague.

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Safety

Patients were more likely than researchers to have safety concerns. While no concerns were major, we invite both patients and researchers to discuss their concerns in the forum.

Many patients had minor safety concerns. Please let us know what we can do to further allay your concerns.

How can our protocol best reflect patients' minor safety concerns. Let us know in the forum.

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Cybermonitoring

Researcher Telemedicine Results

Collection Method Yes No Total
Accelerometer -- Peak Activity Index 6 1 7
Accelerometer -- Step Count 3 2 5
Actimeter 4 2 6
MAPS (Movement and Activity in Physical Space) 2 1 3
Telemedicine is a tenet of the TLS mission, and we received strong support for this strategy from both patients and researchers. Please view the full results of the Protocol Builders for the most in-depth display of the data.

Patients were asked extensive questions on how telemedicine can be used in specific cases and with our specific endpoint. Please view the results of the Patient Protocol Builder to see the full data.

Telemonitoring is a pillar of our development process, and we are pleased to see such broad support from our researcher community. Please elaborate on your responses in the forum.

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Visits/Monitoring

We are still compiling data on telemonitoring.

Please check back soon for more.

We have not yet reached a consensus on the trial's monitoring plan. Please submit your ideas through the Protocol Builder or the forum.

Patients were not asked to submit monitoring plan information.

We are still open to your ideas. Feel free to share this page with relevant colleagues by using the links above.

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Data Visualization

We have not yet reached a consensus on our data visualization plan. Please submit your ideas, and feel free to share this page with any interested colleagues.

See what people are saying about data visualization in the forum by clicking the comments button below.

We encourage further input. Please join the discussion in the forum.

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