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Protocol Details

An Open-label, Non-Randomized, Single-Arm Pilot Study to Evaluate the Effectiveness of Etidronate Treatment for Arterial Calcifications due to Deficiency in CD73 (ACDC)

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: 80 Years

Referral Letter Required


Population Exclusion(s)



Vascular Calcifications;
Joint Capsule Calcifications;
Inherited Disease

Recruitment Keyword(s)



Arterial Calcification;
CD73 Deficiency

Investigational Drug(s)


Investigational Device(s)



Drug: Etidronate
Device: MRI Scan

Supporting Site

National Heart, Lung and Blood Institute


- 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.


- To see if etidronate is a safe and effective treatment for ACDC.


- People between 18 and 80 years of age who have been diagnosed with ACDC.


-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.

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Inclusion and exclusion criteria are to be assessed at Screening and Baseline prior to starting study drug. Each subject must meet the following criteria to be enrolled in this study:

-Subjects must be diagnosed with ACDC based on genetic tests confirming mutation(s) in NT5E and evidence of lower extremity arterial calcifications.

-Either gender and any ethnic background or race

-Age 18-80 years

-Willingness and legal ability to give and sign informed study consent

-Willingness to travel to NIH and local sites for scheduled protocol studies and treatment


Subjects who meet any of the following criteria will be excluded from the study:

-Subjects not diagnosed with ACDC

-Subjects <18 or >80 years of age

-Subjects who are unable or unwilling to sign an informed consent

-Severe renal impairment (estimated creatinine clearance/eGFR of < 30ml/min calculated using CKD-EPI equation)

-Longstanding diabetes mellitus (more than 10 years)

-Known abnormality of the esophagus that would interfere with the passage of the drug

-Known sensitivity to etidronate


-Any other medical or social condition that, in the opinion of the Principal Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data.

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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.

Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev. 1998 Feb;19(1):80-100.

Russell RG. Bisphosphonates: mode of action and pharmacology. Pediatrics. 2007 Mar;119 Suppl 2:S150-62.

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Principal Investigator

Referral Contact

For more information:

Alessandra Brofferio, M.D.
National Heart, Lung and Blood Institute (NHLBI)
NIHBC 10 - CRC BG RM 5-3142
(301) 496-2634

Katherine Marie Carney
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health
Building 10
Room B1D713
10 Center Drive
Bethesda, Maryland 20892
(301) 402-9841

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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