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

Trial Summary

What is the purpose of this trial?

TACT3a is a double blind, placebo-controlled, randomized trial to test a novel therapy, edetate disodium-based chelation of environmentally acquired toxic metals, to reduce cardiovascular events including amputation in high-risk diabetic patients.

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.

What data supports the effectiveness of the drug edetate disodium for treating critical limb ischemia?

A small pilot study showed that edetate disodium-based infusions might help improve wound healing and quality of life in patients with diabetes and critical limb ischemia, suggesting a potential benefit and preliminary evidence of safety. ^{1 2 3 4 5}

Is chelation therapy with edetate disodium safe for humans?

In a small study with patients having diabetes and critical limb ischemia, edetate disodium-based infusions showed preliminary evidence of safety, with no major adverse cardiovascular events reported during the treatment and follow-up period. However, other sources mention potential toxic effects that could be dangerous, so more research is needed to confirm its safety. ^{1 2 3 5 6}

How does the drug edetate disodium differ from other treatments for critical limb ischemia?

Edetate disodium is unique because it is a chelation therapy that involves intravenous infusions to remove toxic metals from the body, which may improve blood flow and promote wound healing in patients with critical limb ischemia, especially those with diabetes. ^{1 2 3 5 7}

Research Team

Gervasio Lamas, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

The trial to assess chelation therapy 2 (TACT2): Rationale and design. [2023]

3. United States 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). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Edetate Disodium-Based Treatment for Secondary Prevention in Post-Myocardial Infarction Patients. [2019]

5. Australia pubmed.ncbi.nlm.nih.gov

Chelation treatment of atherosclerosis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Chelation therapy to prevent diabetes-associated cardiovascular events. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Chelation therapy of atherosclerosis. [2019]