Arterial Calcification, CD73 Deficiency
Conditions
Keywords
NT5E, Bisphosphonates, Vascular Calcifications, Joint Capsule Calcifications, Inherited Disease
Brief 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.
Detailed description
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 bisphosphonates in general, have proven safe and are well tolerated by most patients. This protocol provides for the administration of etidronate to ACDC patients, for whom no alternative treatment is available. Patients will be examined at the NIH Clinical Center bi-annually for 3 years. The primary objective of this clinical study is to test the effectiveness of etidronate in attenuating the progression of lower extremity arterial calcification and vascular blood flow based on CT calcium score and Ankle Brachial Index (ABI).
Interventions
DRUGEtidronate
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.
DEVICEMRI 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
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) | Ankle-brachial Index (ABI) at rest at pre-treatment, on-treatment and post-treatment of etidronate in participants diagnosed with ACDC. ABI is the ratio of the blood pressure in the lower and upper extremities obtained by dividing the blood pressure in an artery of the ankle by the blood pressure in an artery of the arm. Interpreting ABI values indicate the amount of arterial disease. Interpretation is as follows: \> or equal to 1.3 is noncompressible vessel, \> or equal to 1.0 is normal, 0.9 to 0.99 is borderline or equivocal, 0.7 to 0.89 is mild arterial disease, 0.5 to 0.69 is moderate arterial disease, and \<0.5 is severe arterial disease. |
| Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) | Ankle-brachial Index (ABI) after exercise at pre-treatment, on-treatment and post-treatment of etidronate in participants diagnosed with ACDC. ABI is the ratio of the blood pressure in the lower and upper extremities obtained by dividing the blood pressure in an artery of the ankle by the blood pressure in an artery of the arm. Interpreting ABI values indicate the amount of arterial disease. Interpretation is as follows: \> or equal to 1.3 is noncompressible vessel, \> or equal to 1.0 is normal, 0.9 to 0.99 is borderline or equivocal, 0.7 to 0.89 is mild arterial disease, 0.5 to 0.69 is moderate arterial disease, and \<0.5 is severe arterial disease. |
| Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) | Computed tomography (CT) Calcium Score of lower extremities at pre-treatment, on-treatment and post-treatment of etidronate in participants diagnosed with ACDC. According to Cleveland Clinic, a calcium score uses CT to detect calcium deposits in the coronary arteries of the heart. A higher coronary calcium score indicates a higher chance of significant narrowing in the coronary arteries and a higher risk of future heart attack. The Calcium Score range is as follows: zero is no evidence of Coronary Artery Disease (CAD), 1-10 is minimal evidence of CAD, 11-100 is mild evidence of CAD, 101-400 is moderate evidence of CAD and over 400 is extensive evidence of CAD. We applied the same concept to the arteries of the lower extremities. ACDC participants have an overwhelming amount of calcification in the lower extremity vasculature therefore their Calcium Scores are all out of range at baseline and during the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Hand Joint Calcification Based on Hand X-ray Before and During Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) | Changes in hand joint calcification are based on bilateral hand x-ray before and during Etidronate in participants diagnosed with ACDC as a composite score provided by a radiologist measuring calcium deposit volume (mm\^3), calcium deposit density and number of calcifications observed in each finger joint. This is a new scoring system created by our team for the research study, so it has never been used before and healthy volunteer data is not available. However, healthy volunteers would be expected to have no joint calcifications in their hands, in sharp contrast with what we observe in ACDC patients. Density is subjectively defined as 0 equals no calcification, 1 equals barely visible, 2 equals visible with faint margins, 3 equals moderately dense and 4 equals fully dense. The range for the hand X-ray calcification score in this cohort was 288 (minimum) to 863 (maximum). |
| Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- treatment of Etidronate in Participants Diagnosed With ACDC A symptom-limited treadmill progressive test (Gardner Protocol) with gradual increase in grade will be performed in accordance with standard practice to evaluation exercise capacity and pain on exertion in subjects with decreased peripheral arterial perfusion. This test will use a constant speed of 2 mph and gradual increase in grade of 2% every 2 minutes beginning at 0% grade. METS is a measure of how able a person is to tolerate exercise. No scales exists. METS is calculated by = METs x 3.5 x (your body weight in kilograms) / 200 = calories burned per minute. |
| Simple Disease Activity Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) | Simple Disease Activity Index (SDAI) score at pre-treatment, on-treatment and post-treatment of Etidronate in Participants Diagnosed With ACDC. The SDAI is a standard rheumatoid arthritis scores that provide treatment outcome measures on patient joint swelling and pain as well as participants ability to perform daily activity tasks. The SDAI is the sum of five parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity and level of C-Reactive Protein (mg/dl, normal \<1 mg/dl). Total score is defined as: remission as less than 3, low disease activity is between 3 to 11, moderate disease activity is between 11 to 26 and high disease activity is greater than 26. Maximum score possible score is 86 with high disease activity. |
| Duke Activity Status Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) | Duke Activity Status Index (DASI) score at pre-treatment, on-treatment and post-treatment of Etidronate in Participants Diagnosed With ACDC. The DASI is an assessment tool used to evaluate the functional capacity of patients with cardiovascular disease (CVD), such as coronary artery disease, myocardial infarction, and heart failure. Positive responses are summed up to get a total score, which ranges from 0 to 58.2. Higher scores would indicate a higher functional capacity. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the National Institutes of Health Clinical Care Center at Bethesda, Maryland from August 2012 to August 2021.
Participants by arm
| Arm | Count |
|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) Participants diagnosed with Arterial Calcifications due to Deficiency in CD73 (ACDC) will receive Etidronate. Etidronate will be administered orally at total dose of 20mg/kg daily x 14 days, followed by 10 weeks off study drug (12 weeks = one cycle). Participants may receive up to 12 cycles of etidronate. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 4 / 7 |
Outcome results
Primary
Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC
Ankle-brachial Index (ABI) after exercise at pre-treatment, on-treatment and post-treatment of etidronate in participants diagnosed with ACDC. ABI is the ratio of the blood pressure in the lower and upper extremities obtained by dividing the blood pressure in an artery of the ankle by the blood pressure in an artery of the arm. Interpreting ABI values indicate the amount of arterial disease. Interpretation is as follows: \> or equal to 1.3 is noncompressible vessel, \> or equal to 1.0 is normal, 0.9 to 0.99 is borderline or equivocal, 0.7 to 0.89 is mild arterial disease, 0.5 to 0.69 is moderate arterial disease, and \<0.5 is severe arterial disease.
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment)
Population: One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer. Participants that underwent lower limb revascularization procedures, measurements obtained after the procedure dates were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Side Post-Treatment after Exercise | 0.4077 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Side Pre-Treatment after Exercise | 0.5658 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Side On-Treatment after Exercise | 0.5310 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Side Post-Treatment after Exercise | 0.5031 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Side Pre-Treatment after Exercise | 0.6056 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index After Exercise at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Side On-Treatment after Exercise | 0.5664 score on a scale |
Primary
Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC
Ankle-brachial Index (ABI) at rest at pre-treatment, on-treatment and post-treatment of etidronate in participants diagnosed with ACDC. ABI is the ratio of the blood pressure in the lower and upper extremities obtained by dividing the blood pressure in an artery of the ankle by the blood pressure in an artery of the arm. Interpreting ABI values indicate the amount of arterial disease. Interpretation is as follows: \> or equal to 1.3 is noncompressible vessel, \> or equal to 1.0 is normal, 0.9 to 0.99 is borderline or equivocal, 0.7 to 0.89 is mild arterial disease, 0.5 to 0.69 is moderate arterial disease, and \<0.5 is severe arterial disease.
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment)
Population: One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer. Participants that underwent lower limb revascularization procedures, measurements obtained after the procedure dates were excluded from analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Side Post-Treatment at Rest | 0.5771 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Side Pre-Treatment at Rest | 0.5741 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Side On-Treatment at Rest | 0.5411 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Side Post-Treatment at Rest | 0.5222 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Side Pre-Treatment at Rest | 0.5266 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Ankle-brachial Index at Rest at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Side On-Treatment at Rest | 0.5322 score on a scale |
Primary
Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC
Computed tomography (CT) Calcium Score of lower extremities at pre-treatment, on-treatment and post-treatment of etidronate in participants diagnosed with ACDC. According to Cleveland Clinic, a calcium score uses CT to detect calcium deposits in the coronary arteries of the heart. A higher coronary calcium score indicates a higher chance of significant narrowing in the coronary arteries and a higher risk of future heart attack. The Calcium Score range is as follows: zero is no evidence of Coronary Artery Disease (CAD), 1-10 is minimal evidence of CAD, 11-100 is mild evidence of CAD, 101-400 is moderate evidence of CAD and over 400 is extensive evidence of CAD. We applied the same concept to the arteries of the lower extremities. ACDC participants have an overwhelming amount of calcification in the lower extremity vasculature therefore their Calcium Scores are all out of range at baseline and during the study period.
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment)
Population: One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer. Participants that underwent lower limb revascularization procedures, measurements obtained after the procedure dates were excluded from analysis. ACDC participants have an overwhelming amount of calcification in the lower extremity vasculature therefore their Calcium Scores are all out of range at baseline and during the study period.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Lower Extremity Post-Treatment | 83950 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Lower Extremity Pre-Treatment | 88817 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Lower Extremity On-Treatment | 91454 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Left Lower Extremity Post-Treatment | 94358 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Lower Extremity Pre-Treatment | 80289 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Computed Tomography Calcium Score of Lower Extremities at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Right Lower Extremity On-Treatment | 81641 score on a scale |
Secondary
Changes in Hand Joint Calcification Based on Hand X-ray Before and During Etidronate in Participants Diagnosed With ACDC
Changes in hand joint calcification are based on bilateral hand x-ray before and during Etidronate in participants diagnosed with ACDC as a composite score provided by a radiologist measuring calcium deposit volume (mm\^3), calcium deposit density and number of calcifications observed in each finger joint. This is a new scoring system created by our team for the research study, so it has never been used before and healthy volunteer data is not available. However, healthy volunteers would be expected to have no joint calcifications in their hands, in sharp contrast with what we observe in ACDC patients. Density is subjectively defined as 0 equals no calcification, 1 equals barely visible, 2 equals visible with faint margins, 3 equals moderately dense and 4 equals fully dense. The range for the hand X-ray calcification score in this cohort was 288 (minimum) to 863 (maximum).
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment)
Population: One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Changes in Hand Joint Calcification Based on Hand X-ray Before and During Etidronate in Participants Diagnosed With ACDC | Left Hand Pre-Treatment | 241.16 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Changes in Hand Joint Calcification Based on Hand X-ray Before and During Etidronate in Participants Diagnosed With ACDC | Left Hand On Treatment | 275.15 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Changes in Hand Joint Calcification Based on Hand X-ray Before and During Etidronate in Participants Diagnosed With ACDC | Right Hand Pre Treatment | 255.77 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Changes in Hand Joint Calcification Based on Hand X-ray Before and During Etidronate in Participants Diagnosed With ACDC | Right Hand On Treatment | 360.20 score on a scale |
Secondary
Duke Activity Status Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC
Duke Activity Status Index (DASI) score at pre-treatment, on-treatment and post-treatment of Etidronate in Participants Diagnosed With ACDC. The DASI is an assessment tool used to evaluate the functional capacity of patients with cardiovascular disease (CVD), such as coronary artery disease, myocardial infarction, and heart failure. Positive responses are summed up to get a total score, which ranges from 0 to 58.2. Higher scores would indicate a higher functional capacity.
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment)
Population: One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Duke Activity Status Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Pre-Treatment | 47.2282 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Duke Activity Status Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | On-treatment | 46.6314 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Duke Activity Status Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Post-treatment | 50.8242 score on a scale |
Secondary
Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC
Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- treatment of Etidronate in Participants Diagnosed With ACDC A symptom-limited treadmill progressive test (Gardner Protocol) with gradual increase in grade will be performed in accordance with standard practice to evaluation exercise capacity and pain on exertion in subjects with decreased peripheral arterial perfusion. This test will use a constant speed of 2 mph and gradual increase in grade of 2% every 2 minutes beginning at 0% grade. METS is a measure of how able a person is to tolerate exercise. No scales exists. METS is calculated by = METs x 3.5 x (your body weight in kilograms) / 200 = calories burned per minute.
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment)
Population: One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Left Lower Extremity Pre-Treatment | 6.2514 Metabolic Equivalents |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Left Lower Extremity On-Treatment | 6.2577 Metabolic Equivalents |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Left Lower Extremity Post-Treatment | 6.2888 Metabolic Equivalents |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Right Lower Extremity Pre-Treatment | 6.2514 Metabolic Equivalents |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Right Lower Extremity On-Treatment | 6.2577 Metabolic Equivalents |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Peak Metabolic Equivalents (METS) During Treadmill Test at Pre-treatment, On-treatment and Post- Treatment of Etidronate in Participants Diagnosed With ACDC | Right Lower Extremity Post-Treatment | 6.2888 Metabolic Equivalents |
Secondary
Simple Disease Activity Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC
Simple Disease Activity Index (SDAI) score at pre-treatment, on-treatment and post-treatment of Etidronate in Participants Diagnosed With ACDC. The SDAI is a standard rheumatoid arthritis scores that provide treatment outcome measures on patient joint swelling and pain as well as participants ability to perform daily activity tasks. The SDAI is the sum of five parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity and level of C-Reactive Protein (mg/dl, normal \<1 mg/dl). Total score is defined as: remission as less than 3, low disease activity is between 3 to 11, moderate disease activity is between 11 to 26 and high disease activity is greater than 26. Maximum score possible score is 86 with high disease activity.
Time frame: Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment)
Population: One participant received 11 drug cycles due to discontinuation of the drug by the manufacturer.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Simple Disease Activity Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Pre-Treatment | 18.5919 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Simple Disease Activity Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | On-treatment | 8.2987 score on a scale |
| Etidronate Treatment for Arterial Calcifications Due to Deficiency in CD73 (ACDC) | Simple Disease Activity Index Score at Pre-treatment, On-treatment and Post-treatment of Etidronate in Participants Diagnosed With ACDC | Post-treatment | 5.0098 score on a scale |