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.

Conditions

• Arterial Calcification
• CD73 Deficiency

Interventions

DRUG

Etidronate

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.

DEVICE

MRI Scan

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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  lead NIH

Principal Investigators

• Alessandra Brofferio, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-08-20

Primary Completion

2021-08-06

Completion

2021-08-06

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations