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

• Status: Completed
• Trial end date: 2021-08-06
• Target enrollment: 0
• Participant gender: All

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 calcium for at least 2 hours after taking the study drug.

• 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 arm and leg blood pressure tests to measure pain and blood flow.

• 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Etidronic Acid

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.