ACTHAR GEL for Sarcoidosis-Associated Calcium Dysregulation: An Open-label Pilot Study
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|ClinicalTrials.gov Identifier: NCT02155803|
Recruitment Status : Unknown
Verified January 2015 by Marc A. Judson, MD, Albany Medical College.
Recruitment status was: Not yet recruiting
First Posted : June 4, 2014
Last Update Posted : January 26, 2015
|Condition or disease||Intervention/treatment||Phase|
|Sarcoidosis Hypercalcemia Due to Sarcoidosis||Drug: ACTHAR Gel (adrenocorticotropic hormone)||Phase 2 Phase 3|
Sarcoidosis is a multisystem granulomatous disease of unknown cause. Although sarcoidosis most commonly affects the lung, it may affect any organ. Although corticosteroids are recognized as the drug of choice for sarcoidosis. ACTH(adrenocorticotropic hormone) is the only drug that is FDA-approved for this disorder. However, there is limited data on the efficacy of ACTH for this condition.
Calcium metabolism is disregulated in active sarcoidosis. The primary abnormality in calcium metabolism stems from an increased 1-α hydroxylase activity in sarcoid alveolar macrophages that converts 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D, the active form of the vitamin. This can result in hypercalcemia, hypercalciuria, nephrocalcinosis, nephrolithiasis, interstitial nephritis, glomerulonephritis, acute and chronic kidney disease. Importantly, almost of the renal manifestations stem from disordered calcium metabolism. Unlike other organ manifestations of sarcoidosis, the disorder of calcium metabolism is more common in whites compared to african americans.Compared to hypercalcemia, hypercalciuria is three times more common in sarcoidosis, nevertheless, it has largely been ignored.
In general, the patient with hypercalcemia should be advised to avoid sunlight, curtail intake of major sources of dietary calcium and vitamin D, and drink ample fluids.If the patient is symptomatic, serum calcium is greater than 11 mg/dl, the serum creatinine is elevated, or the patient has nephrolithiasis, drug therapy is usually required. The drug of choice is prednisone at an initial daily dose of 20 - 40 mg/day.Unfortunately, prolonged corticosteroid therapy may result in unacceptable side effects including osteoporosis. This is particularly important as elevated calcitriol observed in patients with sarcoidosis can further jeopardize bone structure by resorption. Alternative medications that have shown benefit for sarcoidosis associated calcium dysregulation have included chloroquine,hydroxychloroquine, ketoconazole.
Not only may ACTHER GEL have obvious anti-inflammatory effects by resulting in corticosteroid production, but it may also activate melanocortin receptors. The melanocortin system has powerful anti-inflammatory properties that may be beneficial in the treatment of sarcoidosis.
We believe that there are several specific advantages of assessing the effectiveness of anti-sarcoidosis therapy by examining sarcoidosis-associated disorders of calcium metabolism.
- The measures of granulomatous activity (serum calcium, urinary calcium, serum 25-hydroxyvitamin D, and serum 1, 25-dihydroxyvitamin D levels) are directly related to the granulomatous inflammation of sarcoidosis.
- These parameters can be accurately and objectively quantified. This is an important issue in sarcoidosis as the endpoint for involvement of the lungs, skin, and eyes is problematic because it is either inexact and/or not unidimensional.
These constituents can be easily used to clinically monitor sarcoidosis. This is not the case for other forms of sarcoidosis including involvement of the lung and skin.
- Although hypercalciuria and disordered calcium metabolism is not as common a manifestation of sarcoidosis as lung involvement, there is little evidence that the anti-granulomatous response to this disease is organ specific. In a randomized double-blind placebo control trial of infliximab for pulmonary sarcoidosis, extrapulmonary sarcoidosis also responded to this therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||ACTHAR GEL for Sarcoidosis-Associated Calcium Dysregulation: An Open-label Pilot Study|
|Study Start Date :||February 2015|
|Estimated Primary Completion Date :||June 2015|
|Estimated Study Completion Date :||November 2015|
Experimental: Sarcoidosis related Calcium Dysregulation
Subjects with Sarcoidosis associated calcium dysregulation will be administered 80 units of Acthar Gel (adrenocorticotropic hormone) twice a week for 12 weeks. Clinical visits will be scheduled for -30 days, day of 1st dose and 4,8,12 and 16 week after 1st dose to monitor the health of subjects.
Drug: ACTHAR Gel (adrenocorticotropic hormone)
ACTHAR GEL (adrenocorticotropic hormone) 80 units subcutaneously twice weekly for 12 weeks
- Reduction of 24 hour urine calcium [ Time Frame: Between week 0 and week 12. ]Reduction of 24 hour urine calcium in patients with sarcoidosis associated hypercalciuria (primary endpoint) between week 0 and week 12.
- Change in serum calcium during 12 week ACTHAR GEL treatment [ Time Frame: Baseline compared to 12 weeks. ]
- Change in 1,25 di-hydroxy Vitamin D during 12 week ACTHAR GEL treatment [ Time Frame: Baseline compared to 12 weeks. ]
- Change in patient global VAS during 12 week ACTHAR GEL treatment [ Time Frame: Baseline to 12 weeks ]
- Change in physician global VAS during 12 week ACTHAR GEL treatment [ Time Frame: Baseline to 12 Weeks ]
- Change in urinary symptoms during 12 week ACTHAR GEL treatment [ Time Frame: Baseline to 12 Weeks ]
- Change in Short Form-36 during 12 week ACTHAR GEL treatment [ Time Frame: Baseline to 12 Weeks ]
- Change in Sarcoidosis Health Questionnaire during 12 week ACTHAR GEL treatment [ Time Frame: Baseline to 12 Weeks ]
- Change in eCOST during 12 week ACTHAR gel treatment [ Time Frame: Baseline to 12 Weeks ]
- Change in adjusted eCOST (eCOSTadj) calculated as the eCOST/# organs with an eCOST score > 022 during 12 week ACTHAR gel treatment [ Time Frame: Baseline to 12 Weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02155803
|Contact: Haroon Chaudhry, MBBSfirstname.lastname@example.org|
|Contact: Marc A. Judson, MDemail@example.com|
|United States, New York|
|Albany Medical College||Not yet recruiting|
|Albany, New York, United States, 12208|
|Contact: Haroon Chaudhry, MBBS 518-262-1542 firstname.lastname@example.org|
|Principal Investigator: Marc A. Judson, MD|
|Principal Investigator:||Marc A Judson, MD||Albany Medical College|