CNS Sarcoidosis
Conditions
Brief summary
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.
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.
Interventions
DRUGH.P. Acthar Gel
80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12
Sponsors
University of Maryland, Baltimore
Mallinckrodt
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Karnofsky Performance Status (KPS) Score | 12 months (intention to treat) | The Karnofsky Performance Scale score allows patients to be classified as to their functional impairment. This can be used to compare the effectiveness of different therapies and to assess the prognosis in individual patients. The scale ranges from 0 to 100. Higher scores are associated with better outcomes. |
| Change in Total Number of New Lesions | 1 year | Change in the total number of lesions assessed at 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-Determined Disease Steps (PDDS) | 12 months (intention to treat) | A patient-reported measure of disability which consists of a scale with 9 levels of disability ranging from 0 to 8 (higher scores are associated with worse disability). |
| Montreal Cognitive Assessment (MoCA) | 12 months | The MoCA is a 30-point test that screens for cognitive impairment. Scores range from 0 to 30, with higher scores associated with a better outcome. |
| Symbol-Digit Modalities Test (SDMT) | 12 months (intention to treat) | Assesses cognitive function. The patient is given a set of symbols, and each symbol is paired with a number. The patient is given 90 seconds to write down the number that corresponds to each symbol.Scores range from 0 to 110. A higher score is associated with a better outcome. |
| Work Productivity and Activities Impairment -General Health (WPAI-GH) | 12 months (intention to treat) | The WPAI-GH consists of six questions: 1 = currently employed; 2 = hours missed due to health problems; 3 = hours missed for other reasons; 4 = hours actually worked; 5 = degree that the patient's health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6 = degree health affected productivity in regular unpaid activities (VAS). The result for question 5 is used for the outcome measure, for which a higher number is associated with a worse outcome. |
| Beck Depression Inventory | 12 months (intent to treat) | The Beck Depression Inventory measures the severity of depression in adolescents and adults. It consists of 21 subscales, and the score for each individual subscale is added to give a total score of between 0 to 63. Total scores \<= 10 are considered normal. Scores \> 10 are considered abnormal, with higher scores above that cutoff being associated with a worse outcome. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORHorea Rus
University of Maryland, Baltimore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| H.P. Acthar Gel H.P. Acthar Gel: 80 IU subcutaneously daily for 10 days then followed by 80 IU subcutaneously three times per week through Month 12 | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | H.P. Acthar Gel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 46.3 years |
| Karnofsky Performance Status (KPS) score | 76.67 units on a scale STANDARD_DEVIATION 15.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Total Number of Lesions
Total number of lesions assessed at 1 year
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| H.P. Acthar Gel | Total Number of Lesions | 5 lesions |
Secondary
Quality of Life Measure
Treatment Satisfaction Questionnaire for Medication (TSQM) scores at 4 weeks and change in TSQM scores at 6 months and 12 months versus baseline
Time frame: 6 months and 12 months
Secondary
Quality of Life Measures
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
Time frame: 4 weeks, 6 months and 12 months
Other Pre-specified
Serum and Cerebrospinal Fluid Immune Markers
Change in levels of serum and cerebrospinal fluid immune markers at 4 weeks, 6 months and 12 months versus baseline
Time frame: 4 weeks, 6 months and 12 months