Etidronate for Arterial Calcifications Due to Deficiency in CD73 (ACDC)

Summary

Background: * Arterial Calcifications due to Deficiency in CD73 (ACDC) is a rare genetic disease. People with ACDC develop calcification in the arteries of the lower extremities as well as calcium deposit in the joints of the fingers, wrists, ankles and feet. The lower extremities calcification causes claudication because of severe ischemia requiring at time revascularization procedures. the calcium deposits in the joints causes severe debilitating pain in the hands and feet. Currently, there are no standard treatments for ACDC. * Etidronate is a bisphosphonate that interferes with bone metabolism. It is approved to treat Paget's disease, a condition in which the bones are soft and weak and may be deformed, painful, or easily broken. It is also used to treat high blood calcium levels. Researchers want to see if it can be used to treat the calcifications of ACDC and improve pain and blood flow in the lower extremities and arthritic pain of the hands and feet. Objectives: \- To see if etidronate is a safe and effective treatment for ACDC. Eligibility: \- People between 18 and 80 years of age who have been diagnosed with ACDC. Design: * Participants will be screened with a physical exam and medical history. They will also have imaging studies, including CT scan of the lower extremities, x-rays and DEXA bone scans, before starting treatment. Blood and urine samples will be collected. An exercise tolerance test will also be given and ABI (ankle brachial index will be measured. * Participants will take etidronate by mouth once a day for 14 days every 3 months. They will be assigned an individualized 6- month drug schedule to follow. * Participants will have regular study visits throughout the treatment period. These visits will involve imaging studies, full dental exams, and blood and urine tests. Participants will also have exercise tolerance tests and ABIs measured. * Participants may also provide tissue samples for further study. * Treatment will continue for up to 3 years as long as the side effects are not severe and the condition does not become worse. Participants will have a final follow-up visit after stopping treatment.

Timeline

Start

2012-08-20

Primary completion

2021-08-06

Completion

2021-08-06

Publications

• Background St Hilaire C, Ziegler SG, Markello TC, Brusco A, Groden C, Gill F, Carlson-Donohoe H, Lederman RJ, Chen MY, Yang D, Siegenthaler MP, Arduino C, Mancini C, Freudenthal B, Stanescu HC, Zdebik AA, Chaganti RK, Nussbaum RL, Kleta R, Gahl WA, Boehm M. NT5E mutations and arterial calcifications. N Engl J Med. 2011 Feb 3;364(5):432-42. doi: 10.1056/NEJMoa0912923.
• Background Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev. 1998 Feb;19(1):80-100. doi: 10.1210/edrv.19.1.0325. No abstract available.
• Background Russell RG. Bisphosphonates: mode of action and pharmacology. Pediatrics. 2007 Mar;119 Suppl 2:S150-62. doi: 10.1542/peds.2006-2023H.
• Ferrante EA, Cudrici CD, Rashidi M, Fu YP, Huffstutler R, Carney K, Chen MY, St Hilaire C, Smith K, Bagheri H, Katz JD, Ferreira CR, Gahl WA, Boehm M, Brofferio A. Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC). Vasc Med. 2024 Jun;29(3):245-255. doi: 10.1177/1358863X241235669. Epub 2024 Apr 3.
• Snijders BM, Mathijssen G, Peters MJ, Emmelot-Vonk MH, de Jong PA, Bakker S, Crommelin HA, Ruigrok YM, Brilstra EH, Schepers VP, Spiering W, van Valen E, Koek HL. The effects of etidronate on brain calcifications in Fahr's disease or syndrome: rationale and design of the randomised, placebo-controlled, double-blind CALCIFADE trial. Orphanet J Rare Dis. 2024 Feb 7;19(1):49. doi: 10.1186/s13023-024-03039-7.

Drugs

Indications