Effects of IV-Administered Ca-DTPA and Zn-DTPA To Treat Patients With Gadolinium Deposition Disease

Study Overview
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Brief Summary
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Purpose: There are two goals we have for this prospective single arm study; to see an increase in the amount of gadolinium in 24 hour urine collection following each infusion treatment with Calcium and Zinc DTPA, and to see a reduction or elimination of gadolinium deposition disease (GDD) symptoms. Participants: Twenty (20) patients who are suffering from gadolinium deposition disease (GDD) Procedures: Over a series of three (3) treatment time-points patients will be treated with IV Ca-DTPA on day one, and Zn-DTPA on day two.

Official Title
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Investigator Initiated Investigational New Drug Application to Study the Effects of IV-Administered Ca-DTPA and Zn-DTPA To Treat Patients With Gadolinium Deposition Disease

Conditions
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Headache, Cognitive Disturbance, Skin Hyperpigmentation, Arthralgia

Intervention / Treatment
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* Drug: Calcium DTPA
* Drug: Zinc DTPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Exhibiting 3 or greater of the following symptoms which must be present after having been administered a GBCA: Cognitive disturbance Extremity pain Headache Chest wall pain Skin induration Skin hyperpigmentation Skin pain Arthralgia Exclusion Criteria: Pregnant or lactating Less than 18 years old No evidence of gadolinium (has to have shown previous demonstration of Gd by urine analysis or bone biopsy) Known connective tissue disease such as Systemic Lupus Erythematosus or Scleroderma Severe hemochromatosis or Wilson's disease Glomerular Filtration Rate (GFR) ≤ 60 Have had an investigational drug within last 30 days Unable to give written consent Multiple Sclerosis Chronic heart failure Cirrhosis of the liver

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcium DTPA followed by Zinc DTPA<br>Subjects will receive IV administration of Ca-DTPA on Day 1 and Zn-DTPA on Day 2 at each of treatment time-points. Three identical treatment time-points are scheduled on Month 1, Month 2 and Month 3. | Drug: Calcium DTPA<br>* On Day 1, 2.5 mL of Ca-DTPA (1 g/5 mL) will be administered over a period of 1 minute. A solution of normal saline will then be administered at a rate of 300 mL/hr over 30 minutes. Patients will be seated with hands lowered to their sides to allow the chelator to dwell slightly in the soft tissues of the hands and feet. Patients will then be moved to a supine position and the infusion rate increased to 750 mL/hr over the next 60 minutes. At 90 minutes the remaining 2.5 mL of Ca-DTPA will administered IV over a period of 1 minute, and the normal saline will continue for the remaining 9 minutes. The IV line will then be removed. Patients will be instructed to drink plenty of fluids that evening. The same treatment therapy will consist of 3 time-points, approximately 1 month apart.<br>* Other names: Pentetate calcium trisodium injection;Drug: Zinc DTPA<br>* On Day 2, 2.5 mL of Zn-DTPA (1 g/5 mL) will be administered over a period of 1 minute. A solution of normal saline will then be administered at a rate of 300 mL/hr over 30 minutes. Patients will be seated with hands lowered to their sides to allow the chelator to dwell slightly in the soft tissues of the hands and feet. Patients will then be moved to a supine position and the infusion rate increased to 750 mL/hr over the next 60 minutes. At 90 minutes the remaining 2.5 mL of Zn-DTPA will administered IV over a period of 1 minute, and the normal saline will continue for the remaining 9 minutes. The IV line will then be removed. Patients will be instructed to drink plenty of fluids that evening. The same treatment therapy will consist of 3 time-points, approximately 1 month apart.<br>* Other names: Pentetate zinc trisodium injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 1 in Gd Level From 24-hour Urine Samples Following Calcium DTPA Administration. |  | Baseline, Month 1 | 
| Change From Baseline to Month 1 in Gd Level From 24-hour Urine Samples Following Zinc DTPA Administration. |  | Baseline, Month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Month 2 in Gd Level From 24-hour Urine Samples Following Calcium DTPA Administration. |  | Baseline, Month 2 | 
| Change From Baseline to Month 2 in Gd Level From 24-hour Urine Samples Following Zinc DTPA Administration. |  | Baseline, Month 2 | 
| Change From Baseline to Month 3 in Gd Level From 24-hour Urine Samples Following Calcium DTPA Administration. |  | Baseline, Month 3 | 
| Change From Baseline to Month 3 in Gd Level From 24-hour Urine Samples Following Zinc DTPA Administration. |  | Baseline, Month 3 | 
| Change From Baseline to Month 1 in the Pain Score | Patient self-reported pain scores assessed using a Visual Analog Scale (VAS) ranging from 0 to 10 where 0 indicates no pain, 4 through 6 reflect moderate pain, and 10 reflects worst possible pain. | Baseline, Month 1 (Day 7) | 
| Change From Baseline to Month 2 in the Pain Score | Patient self-reported pain scores assessed using a VAS ranging from 0 to 10 where 0 indicates no pain, 4 through 6 reflect moderate pain, and 10 reflects worst possible pain. | Baseline, Month 2 (Day 7) | 
| Change From Baseline to Month 3 in the Pain Score | Patient self-reported pain scores assessed using a VAS ranging from 0 to 10 where 0 indicates no pain, 4 through 6 reflect moderate pain, and 10 reflects worst possible pain. | Baseline, Month 3 (Day 7) | 
| Change From Baseline to Month 6 in the Pain Score | Patient self-reported pain scores assessed using a VAS ranging from 0 to 10 where 0 indicates no pain, 4 through 6 reflect moderate pain, and 10 reflects worst possible pain. | Baseline, Month 6 | 
| Change From Baseline to Month 12 in the Pain Score | Patient self-reported pain scores assessed using a VAS ranging from 0 to 10 where 0 indicates no pain, 4 through 6 reflect moderate pain, and 10 reflects worst possible pain. | Baseline, Month 12 | 
| Change in American Chronic Pain Association (ACPA) Quality of Life (QOL) Score From Baseline to Month 1 | The ACPA QOL is a self-administered questionnaire measuring functionality for people with pain which looks at the ability to function, rather than pain alone and is intended to measure activity levels. The ACPA QOL consists of 10 possibilities ranging from 0 to 10 where 0 represents Non-functioning and 10 represents Normal Quality of Life. | Baseline, Month 1 (day 7) | 
| Change in ACPA QOL Score From Baseline to Month 2 | The ACPA QOL is a self-administered questionnaire measuring functionality for people with pain which looks at the ability to function, rather than pain alone and is intended to measure activity levels. The ACPA QOL consists of 10 possibilities ranging from 0 to 10 where 0 represents Non-functioning and 10 represents Normal Quality of Life. | Baseline, Month 2 (day 7) | 
| Change in ACPA QOL Score at Month 3 | The ACPA QOL is a self-administered questionnaire measuring functionality for people with pain which looks at the ability to function, rather than pain alone and is intended to measure activity levels. The ACPA QOL consists of 10 possibilities ranging from 0 to 10 where 0 represents Non-functioning and 10 represents Normal Quality of Life. | Baseline, Month 3 (day 7) | 
| Change in ACPA QOL Score at Month 6 | The ACPA QOL is a self-administered questionnaire measuring functionality for people with pain which looks at the ability to function, rather than pain alone and is intended to measure activity levels. The ACPA QOL consists of 10 possibilities ranging from 0 to 10 where 0 represents Non-functioning and 10 represents Normal Quality of Life. | Baseline, Month 6 | 
| Change in ACPA QOL Score at Month 12 | The ACPA QOL is a self-administered questionnaire measuring functionality for people with pain which looks at the ability to function, rather than pain alone and is intended to measure activity levels. The ACPA QOL consists of 10 possibilities ranging from 0 to 10 where 0 represents Non-functioning and 10 represents Normal Quality of Life. | Baseline, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gadolinium, deposition, GBCA, Extremity Pain, Skin Pain, Chest Wall Pain