Etidronate for Arterial Calcifications Due to Deficiency in CD73 (ACDC)
Condition: Arterial Calcification; CD73 Deficiency
MeSH terms: Arteriosclerosis; Calcinosis
Intervention: Etidronate; MRI Scan
Intervention description: Didronel (etidronate disodium)- Didronel tablets contain either 200 mg or 400 mg of etidronate disodium, the disodium salt of (1-hydroxyethylidene) diphosphonic acid, for oral administration. This compound, also known as EHDP. regulates bone metabolism. It is a white powder, highly soluble in water. The 400 mg tablets are white capsule-shaped tablets with ED 400 on one side and G on the other side.; Visit on day 0 and visit at 36 month - Exploratory MRI studies may be employed to evaluate the lumen of the artery and degree of collateral vessels, given that the high degree of calcification is precluding that evaluation by CT.
Intervention MeSH terms: Etidronic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: NT5E; Bisphosphonates; Vascular Calcifications; Joint Capsule Calcifications; Inherited Disease

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

        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

        EXCLUSION CRITERIA

        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

          -  Pregnancy

          -  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.