Clinical Trial I/II Opened, Randomized and Controlled for the Study of the Use of Stem Cells Therapy in Insulinized Diabetic Patients Type 2 With Critical Ischemia in Lower Limbs (CLI): Study of the Needs of Insulin

NCT02287974 | Terminated Phase 1

• 1 other identifier: CeTMMoTa/ICPDI/2010
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

To study the effect of the stem cells therapy autologous mononuclear from the bone marrow, autologous progenitor endothelial CD133 cells from the bone marrow and autologous mesenchymal stem cells from adipose tissue on the inflammatory cytokines, the resistance to insulin and the decrease of the needs of insulin, besides evaluates the safety, viability and efficiency of the intra-arterial infusion of stem cells in diabetic patients type 2 with CLI.

Conditions

Critical Limb Ischemia (CLI)

Outcome Measures

Primary Outcomes (1)

• Serious Adverse Events

  To evaluate the possible complications derived from the procedure (in the first 24 hours after the infusion of stem cells and the incident of Serious Adverse Events and not Serious Adverse Events related to the IMPD or to the procedure of administration

  the entire follow-up period, in the first 24 hours after the infusion of stem cells

Secondary Outcomes (1)

• Efficacy measured by: The changes in the requirements of insulin, Peptide C, Resistance to the insulin, inflammatory Cytokines, pancreatic Reservation, Quantification of the degree of neovascularization (angio/arteriogenesis and vasculogenesis)

  6 months

Study Arms (4)

Autologous mononuclear stem cell from the bone marrow

EXPERIMENTAL

Autologous mononuclear stem cell from the bone marrow in an unique infusion of 150-250 millions of cells

Drug: Stem cell infusion

Autologous endothelial stem cell from the bone marrow

EXPERIMENTAL

Autologous endothelial progenitor CD133 stem cell from the bone marrow in an unique infusion of 2 - 7 millions of CD133 cells

Drug: Stem cell infusion

Autologous mesenchymal stem cells from the adiposite tissue

EXPERIMENTAL

Autologous mesenchymal stem cells from the adipose tissue in an unique infusion of 0.5 millions of cells

Drug: Stem cell infusion

Current medication for the disease

ACTIVE COMPARATOR

Current medication for the disease

Drug: Stem cell infusion

Interventions

Stem cell infusion DRUG

Unique stem cell infusion of the randomized group

Autologous endothelial stem cell from the bone marrow; Autologous mesenchymal stem cells from the adiposite tissue; Autologous mononuclear stem cell from the bone marrow; Current medication for the disease

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤ 85 years
• Diabetic type 2, in treatment with insulin at least 3 previous months.
• Vascular disease infrapopliteal atherosclerotic of severe degree (Patients with category Rutherford-Becker ≥ 4), pretty or bilateral. The critical ischemia of the foot is defined as a persistent / persistent pain that needs analgesia and / or not healing present sores\> 4 weeks, without evidence of improvement with conventional therapies and / or walking test between 1-6 minutes in two ergometries separated at least for 2 weeks and / or index ankle - arm in rest \<0,8.
• Impossibility of revascularization surgical or endovascular or I fail in the surgery of revascularization performed at least 30 days before, with persistence or entry in phase of critical ischemia
• Life expectancy \> 2 years.
• Major amputation is not foreseen in any of the members in the next 6 months after the incorporation.
• Normal Biochemical and bone marrow parameters defined for:
• Leukocytes ≥ 3000
• Neutrophils ≥ 1500
• Platelets ≥ 140000
• AST/ALT ≤ 2,5 standard range institution
• Creatinine ≤2,5 mg/dl and explanation of creatinine ≤ 30 ml/min (MDRD4)
• The women in fertile age will have to obtain negative results in a pregnancy test realized in the moment of the incorporation in the study and promise to use a contraceptive method medically approved while the study lasts.
• Patients who give his Informed Consent in writing for the participation in the study. 10. Patients who have not taken part in another clinical trial in the last 3 months before the incorporation.

You may not qualify if:

• Precedent of neoplasia or hematologic disease (disease myeloproliferative, syndrome myelodysplasic or leukaemia) in the last 2 years.
• Major previous amputation.
• Patients with arterial uncontrolled hypertension (defined as arterial tension\> 180/110 in more than one occasion).
• Cardiac severe insufficiency (NYHA the IVth) or Fraction of Ejection of left ventricle (FAITH) lower than 30 %.
• Patients with ventricular malignant arrhythmias or unstable angina.
• Diagnosis of venous deep thrombosis in 3 previous months.
• Patients with genotype DD of the ECA or genotype E4 of the apo E.
• Concomitant therapy that includes oxygen hyperbaric, vasoactive substances, agents against angiogenesis or inhibiting Cox-II. The agents use is allowed antiplatelets.
• Index of corporal mass\> 40 Kg/m2.
• Patients with the diagnosis of alcoholism in the moment of the incorporation.
• Proliferative Retinopathy without possibility of treatment.
• Diabetic Nephropathy with haemodialysis
• Concomitant disease that reduces the life expectancy to less than 1 years.
• Impossibility foreseen to obtain the inhaled one of 100ml of bone marrow.
• Infection for HIV, Hepatitis B or Hepatitis C.

Sponsors & Collaborators

• Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud: lead
• Iniciativa Andaluza en Terapias Avanzadas: collaborator

Study Sites (2)

Hopsital U. Virgen Macarena

Seville, Seville, 41007, Spain

Location

CABIMER (Andalusian Center for Molecular Biology and Regenerative Medicine)

Seville, 41092, Spain

Location

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Officials

• Bernat Soria

  CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: November 11, 2014
• Study Start: September 1, 2011
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: December 19, 2018

Record last verified: 2018-07

Locations

ES (2)