DTPA (Diethylenetriaminepenta-acetate) Chelation for Symptoms After Gadolinium-assisted MRI Exposure

Study Overview
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Brief Summary
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The study aims at gathering additional data on the safety and effectiveness of using intravenous administration of the drugs Ca-DTPA/Zn-DTPA to remove the heavy metal gadolinium from the bodies of patients who have retained it and developed symptoms of Gadolinium Deposition Disease following an MRI in which a gadolinium-containing contrast agent was utilized. The outcome data will include measures of symptom relief after as many as six paired Calcium-DTPA/Zinc-DTPA chelation treatments. The study also aims at gathering additional data before and after DTPA treatment regarding levels of certain cytokines in the patients' blood that have been reported to be abnormally elevated in patients with retained gadolinium.

Detailed Description
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This study aims at gathering additional data on the safety and effectiveness of using intravenous administration of the drug DTPA to remove the heavy metal gadolinium from the bodies of patients who have retained it and developed symptoms of Gadolinium Deposition Disease following an MRI in which a gadolinium-containing contrast agent was utilized. The outcome data will include measures of symptom relief, including chronic pain, skin changes, and cognitive complaints, after as many as six paired Calcium-DTPA/Zinc-DTPA chelation treatments. The study also aims at gathering additional data before and after DTPA treatment regarding levels of certain cytokines (chemical messengers) in the patients' blood that have been reported to be abnormally elevated in patients with retained gadolinium. DTPA is approved as safe and effective by the federal Food and Drug Administration for the removal of certain radioactive heavy metals, has been in use for more than 60 years, is well tolerated, and has been safely used in three studies, that enrolled 25, 21 and 4 patients respectively who were diagnosed with Gadolinium Deposition Disease.Only the first study reported on symptom improvement, and noted that almost all patients experienced benefit after three paired Calcium-DTPA/Zinc-DTPA chelation treatments.

Official Title
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DTPA Chelation for Symptoms After Gadolinium-assisted MRI

Conditions
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Gadolinium Deposition Disease

Intervention / Treatment
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* Drug: Calcium DTPA and Zinc DTPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 - 65 and able to give informed consent. Have had an MRI with contrast at least 3 months and less than 3 years before study enrollment. Have a 24-hour urine analysis 30 days or more post-MRI that documents abnormally high levels of gadolinium excretion. Exhibit within 30 days of the contrast-assisted MRI new onset of 3 or more of the following symptoms: cognitive disturbance, extremity pain, frequent headaches, chest wall pain, skin induration, skin hyper-pigmentation, skin pain, arthralgia. Have met these Gadolinium Deposition Disease (GDD) diagnostic criteria for at least 3 months. Received the MRI contrast agent Gadobutrol (Gadovist) and no other MRI contrast agents. Exclusion Criteria: Diagnosed by the patient's treating MD with an autoimmune or rheumatological disorder such as systemic lupus, rheumatoid arthritis or scleroderma; diagnosed by the patient's treating MD with a condition or conditions that could cause 3 or more of the 8 diagnostic symptoms of GDD; taking a medication or medications that could cause 3 or more of the 8 diagnostic symptoms of GDD; having a condition or conditions and taking a medication or medications that together might account for the presence of 3 or more of the diagnostic symptoms of GDD. Having Wilson's Disease, hemochromatosis, cancer (other than non-melanoma skin cancer), impaired kidney function, or heart disease compromising cardiac function or causing arrhythmia; Participating in another protocol involving a pharmacological or other treatment of GDD. Suffering from a disorder that could raise particular cytokine levels. In addition to autoimmune and rheumatological conditions, these disorders include diabetes mellitus requiring insulin, chronic fatigue syndrome, active infectious disease, covid infection in the past four months, receipt of blood products in the previous 6 months, major depression, and irritable bowel syndrome. Unable for medical reasons or unwilling to discontinue medications known to lower cytokine levels of interest including: lithium, n-acetylcysteine, aspirin, NSAIDs, sertraline and other Selective Serotonin Reuptake Inhibitor antidepressants, and the over-the-counter supplements ashwagandha, astaxanthin, and milk thistle. Prior chelation treatment for GDD. Pregnant, nursing, intending to become pregnant in the next 6 months, unwilling to utilized an approved, effective contraception method during the study's duration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Six adult patients aged 18 to 65 who meet diagnostic criteria for Gadolinium Deposition Disease and study inclusion criteria, and are free of exclusion criteria will be enrolled.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chelation with open-label Ca-DTPA and Zn-DTPA<br>Six chelation treatments utilizing Ca-DTPA on day 1 and Zn-DTPA on day 2. Paired, 2-chelation day treatments will take place at intervals of one week or more. | Drug: Calcium DTPA and Zinc DTPA<br>* Intravenous administration of 2.5 mL (500 mg) of Ca-DTPA over one minute, followed by 900 mL of normal saline infusion over about 90 minutes, followed by 2.5 mL (500 mg) of Ca-DTPA over one minute, followed by infusion of the remaining 100 mL of normal saline over about 10 minutes. Procedure repeated with Zn-DTPA the following day. Two-day procedure repeated at an interval of one week or more for a total of six 2-day treatment sessions.<br>* Other names: Diethylenetriaminepenta-acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 0-10 Scale of Pain Severity (Higher is more severe pain) | Rating scale of pain severity | 2 days before first DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | 5-6 days after first 2-day DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | 5-6 days after second 2-day DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | 5-6 days after third 2-day DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | 5-6 days after fourth 2-day DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | 5-6 days after fifth 2-day DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | 5-6 days after sixth 2-day DTPA treatment | 
| 0-10 Scale of Pain Severity | Rating scale of pain severity | One month after sixth 2-day DTPA treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gadolinium Deposition Disease Symptom rating scale (higher number = symptom is more troubling0 | Scale rating common symptoms seen in Gadolinium Deposition Disease | 2 days before first DTPA treatment treatment | 
| Gadolinium Deposition Disease Symptom rating scale | Scale rating common symptoms seen in Gadolinium Deposition Disease | 5 to 6 days after first DTPA treatment treatment | 
| Gadolinium Deposition Disease Symptom rating scale | Scale rating common symptoms seen in Gadolinium Deposition Disease | 5 to 6 days after third DTPA treatment treatment | 
| Gadolinium Deposition Disease Symptom rating scale | Scale rating common symptoms seen in Gadolinium Deposition Disease | 5 to 6 days after fourth DTPA treatment treatment | 
| Gadolinium Deposition Disease Symptom rating scale | Scale rating common symptoms seen in Gadolinium Deposition Disease | 5 to 6 days after fifth DTPA treatment treatment | 
| Gadolinium Deposition Disease Symptom rating scale | Scale rating common symptoms seen in Gadolinium Deposition Disease | 5 to 6 days after sixth DTPA treatment treatment | 
| Gadolinium Deposition Disease Symptom rating scale | Scale rating common symptoms seen in Gadolinium Deposition Disease | one month after sixth DTPA treatment treatment | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) (Higher score = more cognitive complaint) | Measure of cognitive function | 2 days before first 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | 5 to 6 after first 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | 5 to 6 after second 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | 5 to 6 after third 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | 5 to 6 after fourth 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | 5 to 6 after fifth 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | 5 to 6 after sixth 2-day DTPA chelation | 
| Cognitive Function - Short Form 8a (Promis Item Bank v2.0) | Measure of cognitive function | one month after sixth 2-day DTPA chelation |