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

• Sponsor: Stanford University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05359835
• Collaborator: (none)
• Enrollment: 5
• Arm: 1
• Anticipated Duration (Months): 17

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gadolinium Deposition Disease	Drug: Calcium DTPA and Zinc DTPA	Early Phase 1

Detailed Description

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Five adult patients aged 18 to 65 who meet diagnostic criteria for Gadolinium Deposition Disease and are free of exclusion criteria will be enrolled.Five adult patients aged 18 to 65 who meet diagnostic criteria for Gadolinium Deposition Disease and are free of exclusion criteria will be enrolled.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: DTPA Chelation for Symptoms After Gadolinium-assisted MRI
• Anticipated Study Start Date: Jul 1, 2022
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Chelation with open-label Ca-DTPA and Zn-DTPA 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; 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.; Other Names: Diethylenetriaminepenta-acetate

Outcome Measures

Primary Outcome Measures

1. 0-10 Scale of Pain Severity (Higher is more severe pain) [2 days before first DTPA treatment]

   Rating scale of pain severity

2. 0-10 Scale of Pain Severity [5-6 days after first 2-day DTPA treatment]

   Rating scale of pain severity

3. 0-10 Scale of Pain Severity [5-6 days after second 2-day DTPA treatment]

   Rating scale of pain severity

4. 0-10 Scale of Pain Severity [5-6 days after third 2-day DTPA treatment]

   Rating scale of pain severity

5. 0-10 Scale of Pain Severity [5-6 days after fourth 2-day DTPA treatment]

   Rating scale of pain severity

6. 0-10 Scale of Pain Severity [5-6 days after fifth 2-day DTPA treatment]

   Rating scale of pain severity

7. 0-10 Scale of Pain Severity [5-6 days after sixth 2-day DTPA treatment]

   Rating scale of pain severity

8. 0-10 Scale of Pain Severity [One month after sixth 2-day DTPA treatment]

   Rating scale of pain severity

Secondary Outcome Measures

1. Gadolinium Deposition Disease Symptom rating scale (higher number = symptom is more troubling0 [2 days before first DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

2. Gadolinium Deposition Disease Symptom rating scale [5 to 6 days after first DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

3. Gadolinium Deposition Disease Symptom rating scale [5 to 6 days after third DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

4. Gadolinium Deposition Disease Symptom rating scale [5 to 6 days after fourth DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

5. Gadolinium Deposition Disease Symptom rating scale [5 to 6 days after fifth DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

6. Gadolinium Deposition Disease Symptom rating scale [5 to 6 days after sixth DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

7. Gadolinium Deposition Disease Symptom rating scale [one month after sixth DTPA treatment treatment]

   Scale rating common symptoms seen in Gadolinium Deposition Disease

8. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) (Higher score = more cognitive complaint) [2 days before first 2-day DTPA chelation]

   Measure of cognitive function

9. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [5 to 6 after first 2-day DTPA chelation]

   Measure of cognitive function

10. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [5 to 6 after second 2-day DTPA chelation]

    Measure of cognitive function

11. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [5 to 6 after third 2-day DTPA chelation]

    Measure of cognitive function

12. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [5 to 6 after fourth 2-day DTPA chelation]

    Measure of cognitive function

13. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [5 to 6 after fifth 2-day DTPA chelation]

    Measure of cognitive function

14. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [5 to 6 after sixth 2-day DTPA chelation]

    Measure of cognitive function

15. Cognitive Function - Short Form 8a (Promis Item Bank v2.0) [one month after sixth 2-day DTPA chelation]

    Measure of cognitive function

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adults aged 18 - 65 and able to give informed consent.

2. Have had an MRI with contrast 30 days or more and less than 6 years before study enrollment.

3. Have a 24-hour urine analysis 30 days or more post-MRI that documents abnormally high levels of gadolinium excretion.

4. Exhibit within 30 days of the contrast-assisted MRI new onset of 3 or more of the following symptoms:

5. cognitive disturbance,

6. extremity pain,

7. frequent headaches,

8. chest wall pain,

9. skin induration,

10. skin hyper-pigmentation,

11. skin pain, h. arthralgia.

12. Have met these Gadolinium Deposition Disease (GDD) diagnostic criteria for at least 4 months.

Exclusion Criteria:

1. Diagnosed by the patient's treating MD with an autoimmune or rheumatological disorder such as systemic lupus, rheumatoid arthritis or scleroderma;

2. 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;

3. taking a medication or medications that could cause 3 or more of the 8 diagnostic symptoms of GDD;

4. 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.

5. Having Wilson's Disease, hemochromatosis, cancer (other than non-melanoma skin cancer), impaired kidney function, or heart disease compromising cardiac function or causing arrhythmia;

6. Participating in another protocol involving a pharmacological or other treatment of GDD.

7. 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.

8. 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.

9. Prior chelation treatment for GDD.

10. Pregnant, nursing, intending to become pregnant in the next 6 months, unwilling to utilized an approved, effective contraception method during the study's duration.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Lorrin M Koran, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Denmark D, Ruhoy I, Wittmann B, Ashki H, Koran LM. Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI. Toxics. 2022 Jan 26;10(2). pii: 56. doi: 10.3390/toxics10020056.
• Goetzl EJ, Maecker HT, Rosenberg-Hasson Y, Koran LM. Altered Functional Mitochondrial Protein Levels in Plasma Neuron-Derived Extracellular Vesicles of Patients With Gadolinium Deposition. Front Toxicol. 2022 Jan 12;3:797496. doi: 10.3389/ftox.2021.797496. eCollection 2021.
• Maecker HT, Siebert JC, Rosenberg-Hasson Y, Koran LM, Ramalho M, Semelka RC. Dynamic Serial Cytokine Measurements During Intravenous Ca-DTPA Chelation in Gadolinium Deposition Disease and Gadolinium Storage Condition: A Pilot Study. Invest Radiol. 2022 Jan 1;57(1):71-76. doi: 10.1097/RLI.0000000000000803.
• Maecker HT, Wang W, Rosenberg-Hasson Y, Semelka RC, Hickey J, Koran LM. An initial investigation of serum cytokine levels in patients with gadolinium retention. Radiol Bras. 2020 Sep-Oct;53(5):306-313. doi: 10.1590/0100-3984.2019.0075.
• Semelka RC, Ramalho M, Jay M, Hickey L, Hickey J. Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients With Presumed Gadolinium Deposition Disease: A Preliminary Report on 25 Patients. Invest Radiol. 2018 Jun;53(6):373-379. doi: 10.1097/RLI.0000000000000453.

• Responsible Party: Lorrin M Koran, MD, Professor of Psychiatry and Behavioral Sciences, Stanford University
• ClinicalTrials.gov Identifier: NCT05359835
• Other Study ID Numbers: 65231
• First Posted: May 4, 2022
• Last Update Posted: May 12, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Edetic Acid; Calcium; Pentetic Acid

Study Results

No Results Posted as of May 12, 2022