Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 12-H-0110 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Background:
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:
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Etidronate Treatment for Arterial Calcifications due to Deficiency in CD73 (ACDC) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etidronate | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
| 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. | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
Not provided
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:
EXCLUSION CRITERIA
Subjects who meet any of the following criteria will be excluded from the study:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Alessandra Brofferio, M.D. | National Heart, Lung, and Blood Institute (NHLBI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21288095 | Background | St Hilaire C, Ziegler SG, Markello TC, Brusco A, Groden C, Gill F, Carlson-Donohoe H, Lederman RJ, Chen MY, Yang D, Siegenthaler MP, Arduino C, Mancini C, Freudenthal B, Stanescu HC, Zdebik AA, Chaganti RK, Nussbaum RL, Kleta R, Gahl WA, Boehm M. NT5E mutations and arterial calcifications. N Engl J Med. 2011 Feb 3;364(5):432-42. doi: 10.1056/NEJMoa0912923. | |
| 9494781 |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
Not provided
Not provided
Participants were recruited at the National Institutes of Health Clinical Care Center at Bethesda, Maryland from August 2012 to August 2021.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
37 months
Adverse events will be captured from the start of the first etidronate administration (day 0) until 30 days following the last dose of treatment. Following this period, any observed or volunteered adverse events will NOT be reported or recorded unless they are greater than Grade 1 and deemed possibly, probably or definitely related to a procedure, test or screening examination that was administered as part of this protocol.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alessandra Brofferio, M.D. | National Heart, Lung, and Blood Institute (NHLBI) | 301.496.2634 | alessandra.brofferio@nih.gov |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 21, 2021 | Feb 16, 2022 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D061205 | Vascular Calcification |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D002114 | Calcinosis |
| D002128 | Calcium Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D012968 | Etidronic Acid |
| D008279 | Magnetic Resonance Imaging |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| MRI Scan | Device | 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. |
|
| Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
| Up to 2 years (pre-treatment), 3 years (on-treatment) |
| 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. | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
| 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. | 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 | 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. | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
| Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev. 1998 Feb;19(1):80-100. doi: 10.1210/edrv.19.1.0325. No abstract available. |
| 17332236 | Background | Russell RG. Bisphosphonates: mode of action and pharmacology. Pediatrics. 2007 Mar;119 Suppl 2:S150-62. doi: 10.1542/peds.2006-2023H. |
| 38568107 | Derived | Ferrante EA, Cudrici CD, Rashidi M, Fu YP, Huffstutler R, Carney K, Chen MY, St Hilaire C, Smith K, Bagheri H, Katz JD, Ferreira CR, Gahl WA, Boehm M, Brofferio A. Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC). Vasc Med. 2024 Jun;29(3):245-255. doi: 10.1177/1358863X241235669. Epub 2024 Apr 3. |
| 38326858 | Derived | Snijders BM, Mathijssen G, Peters MJ, Emmelot-Vonk MH, de Jong PA, Bakker S, Crommelin HA, Ruigrok YM, Brilstra EH, Schepers VP, Spiering W, van Valen E, Koek HL. The effects of etidronate on brain calcifications in Fahr's disease or syndrome: rationale and design of the randomised, placebo-controlled, double-blind CALCIFADE trial. Orphanet J Rare Dis. 2024 Feb 7;19(1):49. doi: 10.1186/s13023-024-03039-7. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | 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. |
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
|
|
|
| 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). | One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to 2 years (pre-treatment), 3 years (on-treatment) |
|
|
|
| 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. | One participant received 11 drug cycles due to discontinuation of the drug by the manufacturer. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
|
|
|
| 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. | One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer. | Posted | Mean | 95% Confidence Interval | score on a scale | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
|
|
|
| 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. | One participant received 11 drug cycles (not 12 cycles) due to discontinuation of the drug by the manufacturer. | Posted | Mean | 95% Confidence Interval | Metabolic Equivalents | Up to 2 years (pre-treatment), 3 years (on-treatment) and up to 1 year (post-treatment) |
|
|
|
| 0 |
| 7 |
| 4 |
| 7 |
| 7 |
| 7 |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| External iliac artery stenosis | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Jump graft on the bypass area declining function of previous graft | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bloating | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Periodontal disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cholesterol high | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypercholesterolemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperphosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Premature atrial contractions | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Left atrial enlargement; Incomplete right bundle branch block | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Chest pain - cardiac | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vivid dreams | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Allergic reaction | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Cholesterol high | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Weight gain | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Calcaneus spur | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Joint inflammation/pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cold symptoms | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Streptococcus pyogenes | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Strep agalactiae Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Malaise | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hemoglobinuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Elevated urine phosphorus | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Renal calculi | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Left inguinal hernia surgery | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia flare swelling of right hand | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia flare swelling of right wrist | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Swelling of finger on fourth MCP of right hand | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hemorrhoids | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Injection site reaction | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blister on right 4th toe | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperparathyroidism | Endocrine disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014054 |
| Tomography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
|
| Right Side Pre-Treatment after Exercise |
|
| Right Side On-Treatment after Exercise |
|
| Right Side Post-Treatment after Exercise |
|
|
| Right Lower Extremity Pre-Treatment |
|
| Right Lower Extremity On-Treatment |
|
| Right Lower Extremity Post-Treatment |
|
|
| Right Hand On Treatment |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
|
| Right Lower Extremity Pre-Treatment |
|
| Right Lower Extremity On-Treatment |
|
| Right Lower Extremity Post-Treatment |
|