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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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)

Brief Summary:

Background:

• Arterial Calcifications due to Deficiency in CD73 (ACDC) is a rare genetic disease. People with ACDC develop calcium deposits in the arteries and joints of the fingers, wrists, ankles and feet. These deposits cause severe pain in the hands and feet, even when the person is at rest, and may lead to loss of the affected hand or foot. Currently, there are no standard treatments for ACDC.
• Etidronate is a drug that helps to slow or stop the natural process that dissolves bone tissue. 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 symptoms of ACDC and improve pain and blood flow in the hands and feet.

Objectives:

- To see if etridronate 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 x-rays and DEXA bone scans, before starting treatment. Blood and urine samples will be collected. An exercise tolerance test will also be given.
• Participants will take etridronate by mouth once a day for 14 days every 3 months. They will be assigned an individualized 6-month drug schedule to follow. Participants should not eat foods that are high in cal
  

  Detailed Summary:

  We have recently identified a novel genetic disease affecting nine known adults in whom de novo vascular calcifications develop in the lower extremity arteries and juxta-articular joint capsules of the fingers, wrists, ankles and feet. This rare disease results from bi-allelic mutations in the gene ecto-5-prime-nucleotidase (NT5E), encoding the CD73 protein. CD73, an enzyme involved in the extracellular ATP metabolic pathway, converts extracellular AMP to adenosine and inorganic phosphate. The clinical symptoms of this rare disease, termed ACDC (Arterial Calcifications due to Deficiency in CD73), include claudication of the calves, thighs, and buttocks, chronic ischemic pain of the feet at rest with threat of potential limb loss, and debilitating rheumatoid pain in the wrists and hands. Radiological and histological evaluations do not resemble classic atherosclerotic vascular calcification, since the calcification and dysplasia in ACDC occur in the medial portion of the arterial blood vessel wall. Data from patient-specific cell lines indicate increased activity of tissue non-specific alkaline phosphatase (TNAP), a key mediator of pathological ectopic tissue calcification, and thus reveals a potential therapeutic target.

  To date, no effective therapy exists for ACDC patients. However, since bisphosphonates are potent competitive inhibitors of TNAP activity and are widely used to modulate bone metabolism, they may beneficially alter vascular calcification. In addition, our preliminary in vitro studies demonstrate the effectiveness of etidronate, a nitrogen-containing bisphosphonate, in lowering TNAP activity in cells isolated from ACDC patients. Etidronate, and bisphophonates in general, have proven safe and well tolerated by most patients.

  This protocol provides for the administration of etidronate to ACDC patients, for wh
  Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
  

  Current Primary Outcome: This study will examine the effectiveness etidronate in attenuating the progression of lower extremity arterial calcification and improved vascular blood flow in subjects diagnosed with the rare disease, ACDC
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome: Functional improvement in treadmill test results; Decrease in hand pain based on Rheumatoid Arthritis assessment tool; Changes in hand joint calcification based on hand x-ray
  
  

  Original Secondary Outcome: Same as current
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: April 24, 2012
  Date Started: April 9, 2012
  Date Completion: December 5, 2017
  Last Updated: May 12, 2017
  Last Verified: December 16, 2016