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

NCT05359835 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 65231
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Gadolinium Deposition Disease

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (15)

• Gadolinium Deposition Disease Symptom rating scale (higher number = symptom is more troubling0

  2 days before first DTPA treatment treatment

• Gadolinium Deposition Disease Symptom rating scale

  5 to 6 days after first DTPA treatment treatment

• Gadolinium Deposition Disease Symptom rating scale

  5 to 6 days after third DTPA treatment treatment

• Gadolinium Deposition Disease Symptom rating scale

  5 to 6 days after fourth DTPA treatment treatment

• Gadolinium Deposition Disease Symptom rating scale

  5 to 6 days after fifth DTPA treatment treatment

Study Arms (1)

Chelation with open-label Ca-DTPA and Zn-DTPA

EXPERIMENTAL

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

Interventions

Calcium DTPA and Zinc DTPA DRUG

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.

Also known as: Diethylenetriaminepenta-acetate

Chelation with open-label Ca-DTPA and Zn-DTPA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Related Publications (5)

• 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.

  PMID: 29419708 BACKGROUND

• 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.

  PMID: 33071374 BACKGROUND

• 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.

  PMID: 34120127 BACKGROUND

• 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.

  PMID: 35295151 BACKGROUND

• 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):56. doi: 10.3390/toxics10020056.

  PMID: 35202243 BACKGROUND

MeSH Terms

Interventions

Pentetic Acid

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids

Study Officials

• Lorrin M Koran, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Sciences

Model Details: 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.

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 4, 2022
• Study Start: April 11, 2023
• Primary Completion: September 12, 2024
• Study Completion: September 13, 2024
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)