- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02298491
CNS Sarcoidosis and Acthar Gel
March 10, 2021 updated by: Horea Rus, University of Maryland, Baltimore
Clinical Biomarkers of Disease Activity and Treatment Responses in Patients With CNS Sarcoidosis Treated With H.P. Acthar Gel
The purpose of this study is to see if treatment with H.P. Acthar® Gel will result in the improvement and long-term stabilization of clinical and radiographic abnormalities that occur in patients with CNS sarcoidosis.
In addition, it will also look at whether treatment will be also associated with improvement in measures of quality of life.
The treatment of CNS sarcoidosis involves the use of either corticosteroids such as prednisone or potent immunosuppressive agents such as methotrexate, both which can induce severe long term side effects.
The adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone (ACTH), which is available for patient use as H.P. Acthar® Gel.
The efficacies of H.P. Acthar® Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been previously studied.
In addition, little is known regarding the expression of immune markers in CNS sarcoidosis and the association of such markers with disease activity and response to treatment.
Study Overview
Detailed Description
Sarcoidosis is a chronic and frequently progressive systemic disease that affects the central nervous system (CNS) in approximately 5% of patients.
The hallmark of the disease is the development of chronic inflammation with formation of non-caseating granulomas that can involve the brain parenchyma and meninges and appear as contrast-enhancing mass lesions on magnetic resonance imaging.
The granulomas are primarily comprised of proinflammatory T cells (Th1 cells and Th17 cells) and macrophages which accumulate during the early stages of granuloma formation.
The inflammation that is generated by these cells is modulated by anti-inflammatory responses mediated by Th2 cells and regulatory T (Treg) cells that later appear and populate the outer regions of the granuloma.
The presence of Treg cells are of particular interest since these cell are also detected in high numbers in peripheral blood and the immune suppression that results may underlie the occurrence of anergy in patients with the disease.
The treatment of CNS sarcoidosis involves the use of either corticosteroids or potent immunosuppressive agents, both which can induce severe long-term side effects.
The adverse effects of steroids may be avoided by treatment with adrenocorticotropic hormone (ACTH), which is available for patient use as H.P. Acthar® Gel.
The efficacy of H.P. Acthar® Gel in the treatment of CNS sarcoidosis and the impact on quality of life have not been previously examined.
In addition, little is known regarding the expression of immune markers in CNS sarcoidosis and the association of such markers with disease activity and response to treatment.
These issues, therefore, will be explored in the context of this proposal.
Study Type
Interventional
Enrollment (Actual)
4
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21201
- University of Maryland, Baltimore
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- A highly probable diagnosis of sarcoidosis, as determined using the World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG) Sarcoidosis Organ Assessment Instrument (Judson et al., 2014), with involvement not limited to the central nervous system.
- At the time of enrollment, a history of clinical deterioration based on the development of new symptoms or worsening previously present symptoms with confirmation by clinical examination and objective clinical testing.
- If on steroids, on a stable dose of the medication for at least 3 months.
Exclusion Criteria:
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: H.P. Acthar Gel
|
80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Number of Lesions
Time Frame: 1 year
|
Total number of lesions assessed at 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life Measures
Time Frame: 4 weeks, 6 months and 12 months
|
Change in Patient Determined Disease Steps (PDDS), Montreal Cognitive Assessment (MoCA), Symbol-Digit Modalities Test (SDMT), Short Form -36 Health Survey (SF-36), Work Productivity and Activities Impairment -General Health (WPAI-GH) and Beck Depression Inventory-II (BDI-II) at 4 weeks, 6 months and 12 months relative to baseline
|
4 weeks, 6 months and 12 months
|
Quality of Life Measure
Time Frame: 6 months and 12 months
|
Treatment Satisfaction Questionnaire for Medication (TSQM) scores at 4 weeks and change in TSQM scores at 6 months and 12 months versus baseline
|
6 months and 12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum and Cerebrospinal Fluid Immune Markers
Time Frame: 4 weeks, 6 months and 12 months
|
Change in levels of serum and cerebrospinal fluid immune markers at 4 weeks, 6 months and 12 months versus baseline
|
4 weeks, 6 months and 12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Horea Rus, University of Maryland, Baltimore
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Curr Opin Pulm Med. 2002 Sep;8(5):435-40. doi: 10.1097/00063198-200209000-00016.
- Arnason BG, Berkovich R, Catania A, Lisak RP, Zaidi M. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis. Mult Scler. 2013 Feb;19(2):130-6. doi: 10.1177/1352458512458844. Epub 2012 Oct 3.
- Co DO, Hogan LH, Il-Kim S, Sandor M. T cell contributions to the different phases of granuloma formation. Immunol Lett. 2004 Mar 29;92(1-2):135-42. doi: 10.1016/j.imlet.2003.11.023.
- Judson MA, Costabel U, Drent M, Wells A, Maier L, Koth L, Shigemitsu H, Culver DA, Gelfand J, Valeyre D, Sweiss N, Crouser E, Morgenthau AS, Lower EE, Azuma A, Ishihara M, Morimoto S, Tetsuo Yamaguchi T, Shijubo N, Grutters JC, Rosenbach M, Li HP, Rottoli P, Inoue Y, Prasse A, Baughman RP, Organ Assessment Instrument Investigators TW. The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis. 2014 Apr 18;31(1):19-27.
- Miller DH, Kendall BE, Barter S, Johnson G, MacManus DG, Logsdail SJ, Ormerod IE, McDonald WI. Magnetic resonance imaging in central nervous system sarcoidosis. Neurology. 1988 Mar;38(3):378-83. doi: 10.1212/wnl.38.3.378.
- Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Kambouchner M, Valeyre D, Chapelon-Abric C, Debre P, Piette JC, Gorochov G. The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 2006 Feb 20;203(2):359-70. doi: 10.1084/jem.20050648. Epub 2006 Jan 23. Erratum In: J Exp Med. 2006 Feb 20;203(2):477.
- Moller DR. Treatment of sarcoidosis -- from a basic science point of view. J Intern Med. 2003 Jan;253(1):31-40. doi: 10.1046/j.1365-2796.2003.01075.x.
- Royal W 3rd, Mia Y, Li H, Naunton K. Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J Neuroimmunol. 2009 Aug 18;213(1-2):135-41. doi: 10.1016/j.jneuroim.2009.05.012. Epub 2009 Jun 17.
- Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011 Oct 10;11(11):762-74. doi: 10.1038/nri3070.
- Stern BJ, Aksamit A, Clifford D, Scott TF; Neurosarcoidosis Study Group. Neurologic presentations of sarcoidosis. Neurol Clin. 2010 Feb;28(1):185-98. doi: 10.1016/j.ncl.2009.09.012.
- Stern BJ, Krumholz A, Johns C, Scott P, Nissim J. Sarcoidosis and its neurological manifestations. Arch Neurol. 1985 Sep;42(9):909-17. doi: 10.1001/archneur.1985.04060080095022.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2016
Primary Completion (Actual)
November 1, 2020
Study Completion (Actual)
November 1, 2020
Study Registration Dates
First Submitted
November 14, 2014
First Submitted That Met QC Criteria
November 19, 2014
First Posted (Estimate)
November 24, 2014
Study Record Updates
Last Update Posted (Actual)
April 9, 2021
Last Update Submitted That Met QC Criteria
March 10, 2021
Last Verified
March 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HP-00062490
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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