Chelation Therapy for Critical Limb Ischemia

(TACT3a Trial)

Overseen By Francisco Ujueta, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mt. Sinai Medical Center, Miami

Must not be taking: Chelating agents

Disqualifiers: Active infection, Heart failure, Smoking, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 40

Duration: 30 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a treatment called edetate disodium, which removes toxic metals from the body, to determine if it can lower the risk of serious heart problems and amputations in people with diabetes. It focuses on individuals with critical limb ischemia, a severe condition where blood flow to the legs is very restricted. Participants will receive either the treatment or a placebo (a substance with no active ingredients) for comparison. This trial may suit individuals over 50 with diabetes who have had non-healing sores or severe leg pain for at least two weeks and are not candidates for surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have had prior intravenous chelation therapy or oral chelation with an FDA-approved agent, there are specific time restrictions before you can participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that edetate disodium has been used safely in past studies. In one study, patients with diabetes and severe limb issues received up to 50 treatments with this medication, and no serious safety problems were reported. Those who completed the treatment experienced wound healing and improved quality of life. Another study found that edetate disodium was used safely and effectively in similar treatments. Overall, these findings suggest that edetate disodium is generally well-tolerated. As this is a Phase 3 trial, the treatment has been tested in larger groups, providing more safety information. This indicates a strong safety record, although researchers continue to monitor for any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about edetate disodium for treating critical limb ischemia because it offers a unique approach compared to current options like revascularization surgeries and medications to improve blood flow. Unlike these standard treatments, which primarily focus on restoring blood flow mechanically or through pharmaceuticals, edetate disodium works by chelation—removing heavy metals and minerals from the bloodstream, which may help reduce vascular calcification and improve circulation. This novel mechanism of action could provide an alternative for patients who are not candidates for surgery or who have not responded well to existing therapies.

What evidence suggests that edetate disodium might be an effective treatment for critical limb ischemia?

Research has shown that edetate disodium-based chelation therapy may reduce the risk of heart problems in people with diabetes, especially after a heart attack. In this trial, some participants will receive edetate disodium to evaluate its potential benefits. One study showed that this treatment helped save limbs in patients with severe artery blockages in their legs. Another study found it could lower heart-related risks for diabetic patients with artery problems. These findings suggest that edetate disodium might effectively reduce complications and improve health outcomes for high-risk diabetic patients with serious limb issues. ^{1 2 4 6 7}

Who Is on the Research Team?

Gervasio Lamas, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for diabetic patients over 50 with critical limb ischemia, who have severe artery blockages in their legs and are not candidates for surgery. They must have had pain or non-healing wounds due to poor blood flow for at least two weeks. Smokers or those with recent heart failure, severe kidney disease, certain metabolic disorders, active infections, or a history of chelation therapy are excluded.

Inclusion Criteria

I am 50 years old or older.

I have severe narrowing in two or more arteries below my knee confirmed by a scan within the last 6 months.

I have diabetes, as shown by my use of insulin or oral medications, or my blood sugar or HbA1c levels.

Exclusion Criteria

I had surgery to improve blood flow in my legs, neck, or heart less than a week ago.

I have severe pain that can't be controlled with medication.

I am a woman who can become pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 40 active or placebo infusions over 30 weeks

30 weeks

40 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with quarterly contacts until the end of the study

1.25 years

Quarterly contacts

What Are the Treatments Tested in This Trial?

Interventions

• Edetate Disodium
• Placebo

Trial Overview The TACT3a study is testing whether edetate disodium can reduce cardiovascular events including amputation in high-risk diabetic patients with critical limb ischemia. Participants will be randomly assigned to receive either the actual drug or a placebo without knowing which one they're getting (double-blind).

How Is the Trial Designed?

Group I: Active Active Control 1 Intervention

edetate disodium (EDTA)dff active infusion

Group II: Placebo Placebo Group 1 Intervention

Placebo infusion

Edetate Disodium is already approved in United States, European Union for the following indications:

Approved in United States as Edetate Disodium for:

• Lead poisoning
• Cardiovascular events including amputation in high-risk diabetic patients

Approved in European Union as Edetate Disodium for:

• Lead poisoning

Who Is Running the Clinical Trial?

Mt. Sinai Medical Center, Miami

Lead Sponsor

Trials

19

Recruited

4,100+

Published Research Related to This Trial

In a pilot study involving 10 patients with diabetes and critical limb ischemia, edetate disodium-based infusions showed potential benefits, including complete wound healing and improved quality of life, with no major adverse cardiovascular events reported during treatment and follow-up.

The study suggests that edetate disodium may be a safe therapeutic option for patients with severe diabetic limb disease, warranting further investigation in a larger randomized controlled trial (TACT3a) to confirm these preliminary findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limb Preservation Using Edetate Disodium-based Chelation in Patients with Diabetes and Critical Limb Ischemia: An Open-label Pilot Study. Arenas, I., Ujueta, F., Diaz, D., et al.[2020]

There is insufficient evidence to support the effectiveness of chelation therapy with edetate disodium for treating coronary or other arterial atherosclerosis, despite its promotion as a nonsurgical treatment.

The review highlights concerns regarding the clinical efficacy and safety of chelation therapy for atherosclerotic vascular disease, indicating that more research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chelation therapy of atherosclerosis. Rathmann, KL., Golightly, LK.[2019]

Edetate disodium (EDTA) is not an appropriate treatment for atherosclerosis and can pose significant health risks, including toxic effects that may lead to fatal outcomes.

Reliance on chelation therapy like EDTA can delay proper medical investigation and treatment, highlighting the need for caution and awareness regarding its dangers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chelation treatment of atherosclerosis. Magee, R.[2021]

TACT2 is a large clinical trial involving 1000 patients with diabetes and a history of myocardial infarction, testing the effects of 40 weekly infusions of edetate disodium on cardiovascular events over a follow-up period of 2.5 to 5 years.

The trial aims to confirm previous findings that chelation therapy can reduce cardiovascular events, with a focus on understanding whether the benefits are linked to the removal of toxic metals like lead and cadmium from the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The trial to assess chelation therapy 2 (TACT2): Rationale and design. Lamas, GA., Anstrom, KJ., Navas-Acien, A., et al.[2023]

In a study of 633 patients with diabetes who had previously experienced a heart attack, treatment with edetate disodium significantly reduced the risk of serious cardiovascular events compared to placebo, with a hazard ratio of 0.59, indicating a 41% lower risk.

Patients on insulin therapy showed the greatest benefit from edetate disodium treatment, with a 58% reduction in the primary endpoint of cardiovascular events compared to those receiving placebo, suggesting that insulin users may respond better to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible differential benefits of edetate disodium in post-myocardial infarction patients with diabetes treated with different hypoglycemic strategies in the Trial to Assess Chelation Therapy (TACT). Escolar, E., Ujueta, F., Kim, H., et al.[2022]

The Trial to Assess Chelation Therapy was a landmark study that showed edetate disodium therapy can significantly improve cardiovascular outcomes in patients who have had a heart attack, particularly benefiting diabetic patients.

This therapy may serve as a modifiable risk factor for atherosclerosis, potentially offering an effective alternative or complement to current treatments, especially given the high costs associated with diabetes and cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edetate Disodium-Based Treatment for Secondary Prevention in Post-Myocardial Infarction Patients. Lamas, GA., Issa, OM.[2019]

The Trial to Assess Chelation Therapy (TACT) found that chelation therapy with EDTA improved outcomes in patients with cardiovascular disease, particularly showing significant benefits in post-myocardial infarction patients with diabetes.

The results suggest that chelation therapy may help reduce cardiovascular events and all-cause mortality by targeting metal accumulation, which is linked to diabetic atherosclerosis, indicating a potential new treatment avenue for diabetic patients at risk of heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chelation therapy to prevent diabetes-associated cardiovascular events. Diaz, D., Fonseca, V., Aude, YW., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6640880/

Edetate Disodium–Based Treatment in a Patient With ... Edetate disodium–based chelation reduced cardiovascular events, especially in patients with diabetes after myocardial infarction.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32025401/

Limb Preservation Using Edetate Disodium-based ... Methods This was an open-label pilot study in 10 patients with diabetes and critical limb ischemia. Each patient received up to 50 edetate ...

3. cureus.com cureus.com/articles/25772-limb-preservation-using-edetate-disodium-based-chelation-in-patients-with-diabetes-and-critical-limb-ischemia-an-open-label-pilot-study

Limb Preservation Using Edetate Disodium-based ... This was an open-label pilot study in 10 patients with diabetes and critical limb ischemia. Each patient received up to 50 edetate disodium- ...

4. hmpgloballearningnetwork.com hmpgloballearningnetwork.com/site/vdm/content/toxic-metal-chelation-edetate-disodium-patient-diabetes-and-critical-limb-ischemia

Toxic Metal Chelation With Edetate Disodium | VDM The Trial to Assess Chelation Therapy (TACT) demonstrated a reduction in cardiovascular risk with an edetate disodium-based chelation regimen.

5. semanticscholar.org semanticscholar.org/paper/Edetate-Disodium-based-Treatment-in-a-Woman-with-Ujueta-Vozzi/25e6a0f6b9663ecdbc0e9b0813ddcec3058059e9

[PDF] Edetate Disodium-based Treatment in a Woman with ... Edetate Disodium–Based Treatment in a Patient With Diabetes and Critical Limb Ischemia After Unsuccessful Peripheral Arterial Revascularizations: A Case Report.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03982693?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(Pentetic%20Acid))))&rank=6

Trial to Assess Chelation Therapy in Critical Limb Ischemia Active therapy will be the same edetate disodium-based infusion used safely and successfully in a previous published study, Trial to Assess Chelation Therapy ( ...

7. researchgate.net researchgate.net/publication/338200789_Limb_Preservation_Using_Edetate_Disodium-based_Chelation_in_Patients_with_Diabetes_and_Critical_Limb_Ischemia_An_Open-label_Pilot_Study

(PDF) Limb Preservation Using Edetate Disodium-based ... The patients who completed at least 40 infusions showed complete wound healing and improvements in overall quality of life as ascertained by PAD ...