Critical Limb Ischemia and Peripheral Artery DiseasePhase 2ACellDREAM2NCT03968198
Administration of Adipose-derived Stem Cells (ASC) in Patient With Critical Limb Ischemia.
A Phase 2 study testing Autologous ASC (for Adipose-derived Stem/Stroma Cell) in people with Critical Limb Ischemia and Peripheral Artery Disease, run by University Hospital, Toulouse at 1 site in France.
Trial summary
Different types of stem cells have recently been studied in clinical trial on ischemic disease of the heart and muscular arteries. Adipose derived stem cell, have shown in vitro and in vivo models a stronger potential of success in recovering from ischemic disease and oxygenation of the tissues. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Limb Ischemia and Peripheral Artery Disease
- What is being tested?
- Autologous ASC (for Adipose-derived Stem/Stroma Cell)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteFrance
- Study dates
- 4 Mar 2020to 10 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients over 18 years old,
- Rest pain or ischemic ulcers /gangrene of the lower limb, present for at least 15 days, requiring analgesic absorption, with ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg
- Patient with persistent CLI after revascularization will be included if :
- they have severe cardiac, respiratory or renal disease who are at increased risk of complication from surgery or anesthesia, e.g. moderately severe or severe heart failure (NYHA class III or IV), severe or very severe Chronic Obstructive Pulmonary disease or severe renal disease (creatinine clearance <30 mL/minute).
- OR
- there is no option for endovascular or open surgery revascularization ; or poor option (defined by: need for an infra-popliteal by-pass without the availability of autologous great saphenous vein, need for use of great saphenous vein <3 mm in diameter for tibial level bypass based on venous duplex ultrasound, or calcified or small (<2 mm) distal target vessel, or open wound on the receiving site or infrapopliteal PAD)
- Patients who signed the informed consent,
- Patient affiliated to a social security system
Who cannot join
- History of cancer
- Need of a major amputation (amputation at or above the ankle) within 2 weeks,
- Ulcers with exposure of tendons, osteomyelitis, or clinically uncontrolled infection,
- TcPO2 <10 mmHg at rest and < 30 mmHg sitting with legs dependent (very poor vascular reserve),
- Patient under judicial protection,
- Pregnant women,
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- Women of childbearing age without effective contraception.
- Refusal of the patient to participate in the study,
- Positive HIV-1 or 2, Human T Leukemia virus (HTLV)-1 or 2, Hepatite B Virus (HBV) (except vaccine profile), Syphilis (except inactive disease), or Hepatite C Virus (HCV)
- Patients necessitating drugs with inhibitory or stimulatory effect on the growth and multiplication of cells or drugs with immunosuppressive effect: Cyclosporine, Mycophenolate mofetil, Azathioprine, Tacrolimus (systemic), Anthracyclines, Neupogen or equivalent, Etanercept, Interferons, Corticoids at anti-inflammatory doses.
- No possibility of adipose tissue harvest and cell injection in the leg
- Another clinical trial participation (except non interventional studies),
- Patient under judicial protection,
- Pregnant and breastfeeding women,
- Women of childbearing age without effective contraception,
- Lack in understanding the nature and aims of the study and/or difficulties in communication with the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Autologous Transplantation of Adipose Tissue Derived Mesenchymal Stroma/Stem Cells (ASC) in Patients With Critical Limb Ischemia.
Different types of stem cells have recently been studied in clinical trial on ischemic disease of the heart and muscular arteries. Adipose derived stem cell, have shown in vitro and in vivo models a stronger potential of success in recovering from ischemic disease and oxygenation of the tissues. The investigators already shown in a phase I study, that adipose derived mesenchymal cells injected in patients with critical limb ischemia and no option for revascularization, had a very good tolerance and interesting effects on skin oxygenation and healing.
The aim of the present clinical trial is to confirm the efficacy autologous transplantation of adipose tissue derived mesenchymal cells in patients with critical limb ischemia with poor options or no option for revascularization.
Read the detailed description
Lower limbs arteries are a frequent localization of atheroma in elderly people (15-20% after 70 years). The most severe stage of the disease, critical limb ischemia (CLI), defined clinically by the presence of rest pain or ischemic ulcer, has a dramatic prognosis at 12 months, with 30% of the patients alive with an amputation, 20% mortality and only 20% of patients with a resolved disease, independently from the treatment. The only validated treatment for this disease is revascularization by endovascular procedures or open surgery. Patients with no option or poor option (high risk) for revascularization have the worst prognosis.
Current research is focusing on the development of cell-based therapies using different sources of stem cells which can provide revascularization and oxygenation of the tissues. A specific form of stem cells, called Adipose-derived Stem/Stroma Cells (ASC), has shown promise for recovering from ischemic disease like critical limb ischemia (CLI) in preclinical trial and trial in phase I. This study will confirm the efficacy autologous transplantation of adipose tissue derived mesenchymal cells in patients with critical limb ischemia with poor options or no option for revascularization.
This study is a phase II, prospective, multicentric, open trial and no comparative. A maximum of 43 patients will be included in two-stage to receive 90*106 intramuscular injection of ASC. Patients will be followed-up for 6 months.
The primary endpoint is the number of patients alive without major amputation and without critical limb ischemia (defined as the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month).
The secondary endpoints are to evaluate:
- the number of new vessels in the treated limb by standardized angiographic magnetic resonance
- the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure
- the percentage reduction of wound surface and percentage of complete ulcer healing
- the pain reduction by standardized evaluation (visual scale and drug consumption)
- the percentage of wound infection and irritative dermatitis (expected adverse events)
- interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα)measurements in blood samples
- Mesenchymal stem cells MSC trophic factors and immune- modulators (Hepatocyte growth factor (HGF), Vascular Endothelial Growth Factor (VEGF), indoleamine 2, 3-dioxygenase (IDO), Human Leucocyte Antigen G (HLA-G)) in vitro.
- Being tested
- Autologous ASC (for Adipose-derived Stem/Stroma Cell)
- Keywords
- Cell therapy, ASC autologous, CLI, PAD, No option
- Medical subject headings
- Chronic Limb-Threatening Ischemia, Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous ASC (for Adipose-derived Stem/Stroma Cell)Drug
After adipose tissue aspiration (liposuction) by an authorized person, ASCs were isolated and cultured during 14±2 days by the French Blood Establishment. Then, patients receive intramuscular injections of ASCs.
| Study group | Role | What they receive |
|---|---|---|
| ASC (Adipose-derived Stem/Stroma Cells) | Experimental | Patients administrated with autologous ASC in their ischemic inferiors limbs Receives: Drug: Autologous ASC (for Adipose-derived Stem/Stroma Cell) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients alive without major amputation
Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.
Measured: Between 1 and 6 months
Number of patients alive without critical limb ischemia
Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.
Measured: Between 1 and 6 months
Secondary outcomes (8)
New vessels
Blind evaluation of the number of new vessels in the treated limb by standardized angiographic magnetic resonance
Measured: Between 1 and 6 months
Blood flow
Evaluation of the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure.
Measured: Between 1 and 6 months
Wound surface reduction
Percentage reduction of wound surface (standardized layer measurement).
Measured: Between 1 and 6 months
Ulcer healing
Evaluation of percentage of complete ulcer healing.
Measured: Between 1 and 6 months
Pain reduction
Evaluation of pain reduction by standardized evaluation (visual scale and drug consumption).
The visual scale is in a form of plastic ruler and measures the intensity of pain on a scale ranging from 0 (no pain) to 10 (maximum pain).
Measured: Between 1 and 6 months
Wound infection
Percentage of wound infection and irritative dermatitis (expected adverse events)
Measured: Between 1 and 6 months
Immuno measures in blood sample
interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα), will be measured out in blood samples.
Measured: Between 1 and 6 months
Immuno measures in vitro
Mesenchymal stem cells (MSC) trophic factors and immune- modulators (Hepatocyte growth factor (HGF), Vascular Endothelial Growth Factor (VEGF), indoleamine 2, 3-dioxygenase (IDO), Human Leucocyte Antigen G (HLA-G)) will be studied in vitro.
Measured: Between 1 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2019
- Study start4 Mar 2020
- Primary completion10 Mar 2023
- Study completion10 Mar 2023
Why it stopped: organizational difficulties for the collection of adipose tissue and for the supply of the experimental drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Critical Limb Ischemia and Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Etablissement Français du Sang
- Responsible party
- Sponsor
- Investigators
- BURA-RIVIERE Alessandra, PhD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03968198
- Sponsor's protocol ID
- RC31/14/7441
- Acronym
- ACellDREAM2
- Status last verified
- Mar 2023
- First submitted
- 14 May 2019
- Last updated
- 31 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dubsky M, Husakova J, Sojakova D, Fejfarova V, Jude EB. Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers-Do We Have Enough Evidence? Mol Diagn Ther. 2023 Nov;27(6):673-683. doi: 10.1007/s40291-023-00667-w. Epub 2023 Sep 22.
PubMed 37740111
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Transplantation of Adipose Tissue Derived Mesenchymal Stroma/Stem Cells (ASC) in Patients With Critical Limb Ischemia.
- ClinicalTrials.gov ID
- NCT03968198
- Acronym / sponsor ID
- ACellDREAM2 / RC31/14/7441
- Keywords
- Cell therapy, ASC autologous, CLI, PAD, No option
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: organizational difficulties for the collection of adipose tissue and for the supply of the experimental drug
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Etablissement Français du Sang
- Study start
- 4 Mar 2020 (actual)
- Primary completion
- 10 Mar 2023 (actual)
- Study completion
- 10 Mar 2023 (actual)
- First posted
- 30 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Different types of stem cells have recently been studied in clinical trial on ischemic disease of the heart and muscular arteries. Adipose derived stem cell, have shown in vitro and in vivo models a stronger potential of success in recovering from ischemic disease and oxygenation of the tissues. The investigators already shown in a phase I study, that adipose derived mesenchymal cells injected in patients with critical limb ischemia and no option for revascularization, had a very good tolerance and interesting effects on skin oxygenation and healing.
The aim of the present clinical trial is to confirm the efficacy autologous transplantation of adipose tissue derived mesenchymal cells in patients with critical limb ischemia with poor options or no option for revascularization.
Detailed description
Lower limbs arteries are a frequent localization of atheroma in elderly people (15-20% after 70 years). The most severe stage of the disease, critical limb ischemia (CLI), defined clinically by the presence of rest pain or ischemic ulcer, has a dramatic prognosis at 12 months, with 30% of the patients alive with an amputation, 20% mortality and only 20% of patients with a resolved disease, independently from the treatment. The only validated treatment for this disease is revascularization by endovascular procedures or open surgery. Patients with no option or poor option (high risk) for revascularization have the worst prognosis.
Current research is focusing on the development of cell-based therapies using different sources of stem cells which can provide revascularization and oxygenation of the tissues. A specific form of stem cells, called Adipose-derived Stem/Stroma Cells (ASC), has shown promise for recovering from ischemic disease like critical limb ischemia (CLI) in preclinical trial and trial in phase I. This study will confirm the efficacy autologous transplantation of adipose tissue derived mesenchymal cells in patients with critical limb ischemia with poor options or no option for revascularization.
This study is a phase II, prospective, multicentric, open trial and no comparative. A maximum of 43 patients will be included in two-stage to receive 90*106 intramuscular injection of ASC. Patients will be followed-up for 6 months.
The primary endpoint is the number of patients alive without major amputation and without critical limb ischemia (defined as the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month).
The secondary endpoints are to evaluate:
- the number of new vessels in the treated limb by standardized angiographic magnetic resonance
- the blood flow by laser Doppler, transcutaneous pressure of oxygen (TcPO2), ankle pressure
- the percentage reduction of wound surface and percentage of complete ulcer healing
- the pain reduction by standardized evaluation (visual scale and drug consumption)
- the percentage of wound infection and irritative dermatitis (expected adverse events)
- interleukin-1, interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, Tumor Necrosis Factor alpha (TNFα)measurements in blood samples
- Mesenchymal stem cells MSC trophic factors and immune- modulators (Hepatocyte growth factor (HGF), Vascular Endothelial Growth Factor (VEGF), indoleamine 2, 3-dioxygenase (IDO), Human Leucocyte Antigen G (HLA-G)) in vitro.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASC (Adipose-derived Stem/Stroma Cells) | Experimental | Drug: Autologous ASC (for Adipose-derived Stem/Stroma Cell)Patients administrated with autologous ASC in their ischemic inferiors limbs |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients over 18 years old,
- Rest pain or ischemic ulcers /gangrene of the lower limb, present for at least 15 days, requiring analgesic absorption, with ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg
- they have severe cardiac, respiratory or renal disease who are at increased risk of complication from surgery or anesthesia, e.g. moderately severe or severe heart failure (NYHA class III or IV), severe or very severe Chronic Obstructive Pulmonary disease or severe renal disease (creatinine clearance <30 mL/minute).
- OR
- there is no option for endovascular or open surgery revascularization ; or poor option (defined by: need for an infra-popliteal by-pass without the availability of autologous great saphenous vein, need for use of great saphenous vein <3 mm in diameter for tibial level bypass based on venous duplex ultrasound, or calcified or small (<2 mm) distal target vessel, or open wound on the receiving site or infrapopliteal PAD)
Key exclusion criteria (16 listed)
- History of cancer
- Need of a major amputation (amputation at or above the ankle) within 2 weeks,
- Ulcers with exposure of tendons, osteomyelitis, or clinically uncontrolled infection,
- TcPO2 <10 mmHg at rest and < 30 mmHg sitting with legs dependent (very poor vascular reserve),
- Patient under judicial protection,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous ASC (for Adipose-derived Stem/Stroma Cell)After adipose tissue aspiration (liposuction) by an authorized person, ASCs were isolated and cultured during 14±2 days by the French Blood Establishment. Then, patients receive intramuscular injections of ASCs. | Drug | ASC (Adipose-derived Stem/Stroma Cells) |
Primary outcome
Number of patients alive without major amputation
Time frame: Between 1 and 6 months
Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.
Number of patients alive without critical limb ischemia
Time frame: Between 1 and 6 months
Evaluation of the presence of rest pain or ischemic ulcer and ankle pressures less than 70 mmHg or toe systolic pressure less than 50 mmHg or TcPO2 of less than 30 mmHg, at six month.
8 secondary outcomes
New vessels
Time frame: Between 1 and 6 months
Blood flow
Time frame: Between 1 and 6 months
Wound surface reduction
Time frame: Between 1 and 6 months
Ulcer healing
Time frame: Between 1 and 6 months
Pain reduction
Time frame: Between 1 and 6 months
Wound infection
Time frame: Between 1 and 6 months
Immuno measures in blood sample
Time frame: Between 1 and 6 months
Immuno measures in vitro
Time frame: Between 1 and 6 months
Results and safety
The study was stopped early (reason given: organizational difficulties for the collection of adipose tissue and for the supply of the experimental drug). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Derived from this study: PubMed 37740111Dubsky M, Husakova J, Sojakova D, Fejfarova V, Jude EB. Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers-Do We Have Enough Evidence? Mol Diagn Ther. 2023 Nov;27(6):673-683. doi: 10.1007/s40291-023-00667-w. Epub 2023 Sep 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BURA-RIVIERE Alessandra, PhD principal investigator
University Hospital, Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous ASC (for Adipose-derived Stem/Stroma Cell) in people with Critical Limb Ischemia and Peripheral Artery Disease, run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: organizational difficulties for the collection of adipose tissue and for the supply of the experimental drug). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients alive without major amputation (time frame: Between 1 and 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03968198, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2023.