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

• ClinicalTrials.gov Identifier: NCT02947022
• Recruitment Status: Terminated
• First Posted: October 27, 2016
• Results First Posted: April 6, 2018
• Last Update Posted: April 6, 2018
• Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Hameln Pharma GmbH
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Headache; Cognitive Disturbance; Skin Hyperpigmentation; Arthralgia	Drug: Calcium DTPA; Drug: Zinc DTPA	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2016
• Actual Primary Completion Date: January 31, 2017
• Actual Study Completion Date: January 31, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: Calcium DTPA followed by Zinc DTPA; 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; 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.; Other Name: Pentetate calcium trisodium injection; Drug: Zinc DTPA; 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.; Other Name: Pentetate zinc trisodium injection

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Month 1 in Gd Level From 24-hour Urine Samples Following Calcium DTPA Administration. [ Time Frame: Baseline, Month 1 ]
2. Change From Baseline to Month 1 in Gd Level From 24-hour Urine Samples Following Zinc DTPA Administration. [ Time Frame: Baseline, Month 1 ]

Secondary Outcome Measures :

1. Change From Baseline to Month 2 in Gd Level From 24-hour Urine Samples Following Calcium DTPA Administration. [ Time Frame: Baseline, Month 2 ]
2. Change From Baseline to Month 2 in Gd Level From 24-hour Urine Samples Following Zinc DTPA Administration. [ Time Frame: Baseline, Month 2 ]
3. Change From Baseline to Month 3 in Gd Level From 24-hour Urine Samples Following Calcium DTPA Administration. [ Time Frame: Baseline, Month 3 ]
4. Change From Baseline to Month 3 in Gd Level From 24-hour Urine Samples Following Zinc DTPA Administration. [ Time Frame: Baseline, Month 3 ]
5. Change From Baseline to Month 1 in the Pain Score [ Time Frame: Baseline, Month 1 (Day 7) ]
   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".
6. Change From Baseline to Month 2 in the Pain Score [ Time Frame: Baseline, Month 2 (Day 7) ]
   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".
7. Change From Baseline to Month 3 in the Pain Score [ Time Frame: Baseline, Month 3 (Day 7) ]
   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".
8. Change From Baseline to Month 6 in the Pain Score [ Time Frame: Baseline, Month 6 ]
   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".
9. Change From Baseline to Month 12 in the Pain Score [ Time Frame: Baseline, Month 12 ]
   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".
10. Change in American Chronic Pain Association (ACPA) Quality of Life (QOL) Score From Baseline to Month 1 [ Time Frame: Baseline, Month 1 (day 7) ]
    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".
11. Change in ACPA QOL Score From Baseline to Month 2 [ Time Frame: Baseline, Month 2 (day 7) ]
    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".
12. Change in ACPA QOL Score at Month 3 [ Time Frame: Baseline, Month 3 (day 7) ]
    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".
13. Change in ACPA QOL Score at Month 6 [ Time Frame: Baseline, 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".
14. Change in ACPA QOL Score at Month 12 [ Time Frame: Baseline, 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".

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, North Carolina

UNC Hospitals

Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Hameln Pharma GmbH

Investigators

• Principal Investigator: Richard Semelka, MD; University of North Carolina, Chapel Hill

  Study Documents (Full-Text)

Documents provided by University of North Carolina, Chapel Hill:

Study Protocol and Statistical Analysis Plan  [PDF] December 15, 2016

More Information

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02947022
• Other Study ID Numbers: 16-1080
• First Posted: October 27, 2016
• Results First Posted: April 6, 2018
• Last Update Posted: April 6, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of North Carolina, Chapel Hill:

gadolinium; deposition; GBCA; Extremity Pain; Skin Pain; Chest Wall Pain

Additional relevant MeSH terms:

Arthralgia; Hyperpigmentation; Headache; Cognitive Dysfunction; Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Pigmentation Disorders; Skin Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Calcium, Dietary; Zinc; Edetic Acid; Calcium; Pentetic Acid; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Trace Elements; Micronutrients; Antidotes; Protective Agents; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Iron Chelating Agents; Anticoagulants