Multiple SclerosisPhase 4ACTHARNCT03021317
Effects of ACTHAR on Advanced MRI Surrogate Markers of Disease Activity and on Comprehensive Immune Signature During MS Relapses
A Phase 4 study testing ACTHar in people with Multiple Sclerosis, run by University of Chicago.
Trial summary
ACTHAR is a FDA approved drug for MS relapses. The purpose of the study is to examine the efficacy of this agent in improving relapses as measured by advanced MRI and laboratory techniques: 1. Advanced serial MRI studies on patients during and after an acute MS relapse. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- ACTHar
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- No sites listed yet
- Study dates
- 20 Dec 2016to 7 Oct 2020
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age > 18
- undergoing a clinical relapse and associated MRI active lesion
Who cannot join
- Recent infection, any
- use of any glucocorticoid 30 days prior to enrollment
- unable to consent
About this study
ACTHAR is a FDA approved drug for MS relapses. The purpose of the study is to examine the efficacy of this agent in improving relapses as measured by advanced MRI and laboratory techniques:
- Advanced serial MRI studies on patients during and after an acute MS relapse. MRI will be performed at baseline, 1 month after the 1st dose of ACTHAR, and months 3, 6, and 12. ACTHAR will be administered for 10 days. Patients will start ACTHAR within 48 hours of relapse assessment.
- Serial immune assays on patients during and after an acute MS relapse. Serum and blood samples with be collected at baseline, last day of ACTHAR (day 10 of therapy), 1 month post 1st dose, and months 3 and 6.
Read the detailed description
Multiple sclerosis (MS) is a demyelinating disease of the CNS. In a vast majority of patients, its clinical course is characterized by transient attacks of acute neurological compromise, followed by variable degree of recovery. Each relapse leaves a patient with some degree of residual disability. Higher number and longer duration of relapses are associated with greater loss of function. Hence, it is imperative that these relapses are optimally treated and curtailed in duration to allow for maximal recovery and repair.
ACTH (ACTHAR or IV formulation) has long been used for the treatment of MS relapses. ACTH has equivalent efficacy to high-dose IV methylprednisolone in curtailing the duration of MS relapses. ACTH has an advantage over steroids in that it has a short half-life and much less deleterious steroid effect on bone and fat metabolism. Importantly, ACTH has a unique mechanism of action on immune and brain cells through melanocortin receptors (MCRs), which promote production of regulatory and anti-inflammatory cytokines and support oligodendrocyte precursors and neuronal function, all of which could lead to better repair of MS lesions and favorable clinical outcome.
The studies proposed herein will provide a better understanding of the effects of ACTHAR in improving MRI lesion characteristics over time. The complementary immune and genetic studies will further provide evidence for the mechanism of action (MOA) of ACTHAR in improving immune dysfunction related to MS relapse. This is a one of a kind study, involving both advanced/state-of-the art MRI techniques and immune studies to assess the beneficial effects of ACTHAR in MS relapses in the same patients over time.
The primary outcome of all MRI techniques is to determine whether there is an improvement and subsequent stabilization/repair over time of tissue damage caused by inflammatory MS disease activity. Multiple conventional and nonconventional MR imaging modalities are examined here to determine which of these are the most sensitive and reliable in detecting microstructural damage and repair over time. The results of this study will also greatly impact the design of future MS trials by providing a guide for selecting the most appropriate MRI and immune methods to assess treatment efficacy in MS.
In terms of laboratory analysis, the following will be examined:
- Determine immune subset expression in CD4+FOXP3 Tregs and CD8+CD28- T suppressor cells by flow cytometry at each visit.
- Global gene expression profiling in MNC with 913,000 probes at each visit. Bioinformatics will include pathway analysis and ACTHAR-induced RNA signature.
- Serum protein profiling for immune-regulated cytokines (Th1, Th2, Th17, monokines…) and neuroprotective proteins (NGF, BDNF, ACTH, HGF, CNTF, IL-10…) at each visit.
- All data from protein and gene expression, as well as immune subset expression will be compared to our database generated from therapy-naïve stable and exacerbating MS. ACTHAR signature will analyzed based on these comparisons.
- Conditions
- Multiple Sclerosis
- Being tested
- ACTHar
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACTHarDrug
Also called repository corticotropin injection
The patients will be given 80 Units subcutaneously of ACTHAR at the time of MS relapse daily for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Treated Group | Experimental | Open label, single arm treatment study using MRI and laboratory markers to assess efficacy of ACTHAR in MS patients who are undergoing relapses. Receives: Drug: ACTHar |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in T1 Lesion Relaxation Time
T1 relaxation time is a MRI marker of injury. The change in this metric will be followed over 12 months to see if lesions recover post ACTHAR intervention.
Measured: 12 month after the completion of intervention
Secondary outcomes (1)
Change in Immune Subset Expression in CD4+FOXP3 Tregs by Flow Cytometry Post ACTHAR Intervention
Treg cells are unregulated during the healing process in MS relapses. Changes in this population of immune cells will be measured over a course of 6 months post ACTHAR intervention.
Measured: 6 month after the completion of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2017 (estimated)
- Study start20 Dec 2016
- Primary completion7 Oct 2020
- Study completion7 Oct 2020
Why it stopped: Terminated early due to lack of resources.
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 University of ChicagoThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adil Javed, MD, PhD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03021317
- Sponsor's protocol ID
- IRB16-1390
- Acronym
- ACTHAR
- Status last verified
- May 2024
- First submitted
- 12 Jan 2017
- Last updated
- 16 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of ACTHAR on Advanced MRI Surrogate Markers of Disease Activity and on Comprehensive Immune Signature During MS Relapses
- ClinicalTrials.gov ID
- NCT03021317
- Acronym / sponsor ID
- ACTHAR / IRB16-1390
- Conditions
- Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated early due to lack of resources.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 20 Dec 2016 (actual)
- Primary completion
- 7 Oct 2020 (actual)
- Study completion
- 7 Oct 2020 (actual)
- First posted
- 13 Jan 2017 (estimated)
- Results
- Posted 16 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
ACTHAR is a FDA approved drug for MS relapses. The purpose of the study is to examine the efficacy of this agent in improving relapses as measured by advanced MRI and laboratory techniques:
- Advanced serial MRI studies on patients during and after an acute MS relapse. MRI will be performed at baseline, 1 month after the 1st dose of ACTHAR, and months 3, 6, and 12. ACTHAR will be administered for 10 days. Patients will start ACTHAR within 48 hours of relapse assessment.
- Serial immune assays on patients during and after an acute MS relapse. Serum and blood samples with be collected at baseline, last day of ACTHAR (day 10 of therapy), 1 month post 1st dose, and months 3 and 6.
Detailed description
Multiple sclerosis (MS) is a demyelinating disease of the CNS. In a vast majority of patients, its clinical course is characterized by transient attacks of acute neurological compromise, followed by variable degree of recovery. Each relapse leaves a patient with some degree of residual disability. Higher number and longer duration of relapses are associated with greater loss of function. Hence, it is imperative that these relapses are optimally treated and curtailed in duration to allow for maximal recovery and repair.
ACTH (ACTHAR or IV formulation) has long been used for the treatment of MS relapses. ACTH has equivalent efficacy to high-dose IV methylprednisolone in curtailing the duration of MS relapses. ACTH has an advantage over steroids in that it has a short half-life and much less deleterious steroid effect on bone and fat metabolism. Importantly, ACTH has a unique mechanism of action on immune and brain cells through melanocortin receptors (MCRs), which promote production of regulatory and anti-inflammatory cytokines and support oligodendrocyte precursors and neuronal function, all of which could lead to better repair of MS lesions and favorable clinical outcome.
The studies proposed herein will provide a better understanding of the effects of ACTHAR in improving MRI lesion characteristics over time. The complementary immune and genetic studies will further provide evidence for the mechanism of action (MOA) of ACTHAR in improving immune dysfunction related to MS relapse. This is a one of a kind study, involving both advanced/state-of-the art MRI techniques and immune studies to assess the beneficial effects of ACTHAR in MS relapses in the same patients over time.
The primary outcome of all MRI techniques is to determine whether there is an improvement and subsequent stabilization/repair over time of tissue damage caused by inflammatory MS disease activity. Multiple conventional and nonconventional MR imaging modalities are examined here to determine which of these are the most sensitive and reliable in detecting microstructural damage and repair over time. The results of this study will also greatly impact the design of future MS trials by providing a guide for selecting the most appropriate MRI and immune methods to assess treatment efficacy in MS.
In terms of laboratory analysis, the following will be examined:
- Determine immune subset expression in CD4+FOXP3 Tregs and CD8+CD28- T suppressor cells by flow cytometry at each visit.
- Global gene expression profiling in MNC with 913,000 probes at each visit. Bioinformatics will include pathway analysis and ACTHAR-induced RNA signature.
- Serum protein profiling for immune-regulated cytokines (Th1, Th2, Th17, monokines…) and neuroprotective proteins (NGF, BDNF, ACTH, HGF, CNTF, IL-10…) at each visit.
- All data from protein and gene expression, as well as immune subset expression will be compared to our database generated from therapy-naïve stable and exacerbating MS. ACTHAR signature will analyzed based on these comparisons.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treated Group | Experimental | Drug: ACTHarOpen label, single arm treatment study using MRI and laboratory markers to assess efficacy of ACTHAR in MS patients who are undergoing relapses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- age > 18
- undergoing a clinical relapse and associated MRI active lesion
Key exclusion criteria (3 listed)
- Recent infection, any
- use of any glucocorticoid 30 days prior to enrollment
- unable to consent
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 |
|---|---|---|
| ACTHarAlso: repository corticotropin injectionThe patients will be given 80 Units subcutaneously of ACTHAR at the time of MS relapse daily for 10 days. | Drug | Treated Group |
Primary outcome
Change in T1 Lesion Relaxation Time
Time frame: 12 month after the completion of intervention
T1 relaxation time is a MRI marker of injury. The change in this metric will be followed over 12 months to see if lesions recover post ACTHAR intervention.
1 secondary outcome
Change in Immune Subset Expression in CD4+FOXP3 Tregs by Flow Cytometry Post ACTHAR Intervention
Time frame: 6 month after the completion of intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- 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.
Adil Javed, MD, PhD principal investigator
University of Chicago
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ACTHar in people with Multiple Sclerosis, run by University of Chicago.
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 2 inclusion and 3 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 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 16 May 2024). 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?
Change in T1 Lesion Relaxation Time (time frame: 12 month after the completion of intervention). 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 16 May 2024.