- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT03455335
Autologous Stem Cells for the Treatment of No Option Critical Limb Ischemia
A Phase 1b, Open Label, Uncontrolled, Non-randomized Dose-escalation Study to Examine the Safety of Intramuscular Autologous Transplantation of Escalating Doses of Mesenchymal Stem Cells to Patients With no Option Critical Limb Ischemia.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
This is a phase 1b, open label, uncontrolled, non-randomized dose-escalation study to examine the safety of intramuscular autologous transplantation of escalating doses of mesenchymal stem cells to patients with no option critical limb ischemia.
Trial Aims and Objectives: To examine the safety of intramuscular transplantation of escalating doses of autologous bone marrow derived mesenchymal stem cells to patients with no option critical limb ischemia.
Patient Population: Patients with critical limb ischemia who are not candidates for revascularization.
Trial Setting:HRB Clinical Research Facility Galway and Galway University Hospitals.
Trial Intervention:Intramuscular delivery of autologous bone marrow-derived mesenchymal stem cells to patients with no option critical limb ischemia.
Study Design: Open label, uncontrolled, non-randomized, dose escalation study. Sample Size: 9 Method of Participant Assignment:Sequential administration of 3 escalating doses of autologous bone marrow-derived mesenchymal stem cells.
Examination Points: Day 0, 7, 30, 90, 180, 365 and 730 Primary Outcome: Serious adverse events that are attributable to intervention. Secondary Outcomes :Amputation free survival, median time to amputation, TcPo2, ABI, pain scale, ulcer healing, quality of life assessments, collateral vessel formation detected by MRI at 12 months.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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Galway
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Galway City, Galway, Irland
- Galway University Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
Each patient must meet all of the following inclusion criteria to be enrolled into the study
- Men and women between the ages of 18 and 85
- Voluntary written informed consent, given before performance of any study-related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care
- Presented with CLI with rest pain or ulceration with no option for revascularization agreed by an expert panel including an interventional radiologist and vascular surgeon; CLI defined as persistent ischemic rest pain for greater than or equal to 2 weeks and/or ulceration or gangrene of the toe or foot
- Estimated life expectancy > 6 months as deemed by patient's clinician and/or investigator
- Suitable candidate for a bone marrow aspiration, deemed by Consultant Haematologist
- Chronic critical limb ischaemia with rest pain (Rutherford Class 4) or mild-to-moderate tissue loss (Rutherford Class 5) who are not candidates for revascularisation
- Medically fit to undergo bone marrow harvest and stem cell intramuscular injection
- One of the following haemodynamic parameters: ankle systolic pressure < 70 mmHg or ABI <0.9 TBI <0 .6 TcPO2 <60mmHg on room air
Exclusion Criteria:
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Has received prior therapy with MSCs
- Has had previous amputation of the talus or above
- Has failed revascularization within 2 weeks before entry to the study
- Known Aortoiliac disease with > 50% stenosis
- Contraindication to intramuscular procedure, including active infection in the affected limb, or wet gangrene or exposed bone or tendon in lower limb with CLI, or in the opinion of the attending clinician, is unsuitable for intramuscular procedure
- Severe co-morbidity limiting 6 month survival of patients
- Abnormal liver function as defined by AST and ALT > 2.5 fold the ULN and total bilirubin > 1.5 ULN
- Significant cognitive impairment (Mini Mental Status Examination <22)
- Presence of proliferative retinopathy (in participants with diabetes mellitus only)
- Presence of poorly controlled diabetes mellitus with HbAIc > 10% within previous 3 months
- HIV or HBsAg positive
- Presence of acute coronary syndrome
- Patient has known active malignancy
- Pregnancy
- Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel
- Patient taking other investigational drugs at the time of enrolment or within 28 days of enrolment
- Rutherford class 6 CLI
- Significant bone marrow dysfunction, based on assessment by Haematologist or an established diagnosis of myelodysplasia, or myeloproliferative disorder etc.
- Bleeding diathesis, coagulopathy, thrombocytopenia etc.
- Patients in whom delay incurred by attempts at limb salvage using MSCs will adversely affect prognosis in the opinion of the responsible attending clinician
Patients with known allergy to foetal bovine serum or trypsin
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Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: low dose cohort
20 million hMSCs .
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Andre navn:
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Eksperimentell: mid dose cohort
40 million hMSCs
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Andre navn:
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Eksperimentell: high dose cohort
80 million hMSCs .
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Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
The number of Serious Adverse Events that are attributable to the treatment
Tidsramme: 12 months
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The number of Serious Adverse Events that are attributable to the MScs
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12 months
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The severity of Serious Adverse Events that are attributable to the treatment
Tidsramme: 12 months
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The number of Serious Adverse Events that are attributable to the MScs
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12 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Amputation free survival
Tidsramme: 12 months
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Efficacy measured by the presence or absence of the target limb
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12 months
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median time to amputation,
Tidsramme: 12 months
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Efficacy measured by the duration from time of cell administration to time of amputation if applicable.
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12 months
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Change in Transcutaneous Pressure of Oxygen TcPO2
Tidsramme: 12 months
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Efficacy will be determined by improvement from baseline in mmHg
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12 months
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Change in Ankle Brachial Index
Tidsramme: 12 months
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"Ankle Brachial Index: An indicator of peripheral perfusion measured by dividing Ankle Pressure (mmHg) by brachial pressure (mmHg) (normal ABI is 1.0 ).
Efficacy outcome will be measured by improvement from baseline .
The higher the ABI, the better the outcome."
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12 months
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Collateral vessel formation
Tidsramme: 12 months
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Efficacy will be determined the presence of collateral vessel formation as detected by MRI
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12 months
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Change in Ischemic rest pain
Tidsramme: 12 months.
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Efficacy will be determined by decrease in score from baseline as measured by verbal analogue scale (0 = no pain, 10 = worst pain in life)
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12 months.
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Change in Ulcer size
Tidsramme: 12 months.
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Efficacy will be determined by decrease in the surface area from baseline as measured by ImageJ software and or complete healing of the ulcer
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12 months.
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Change in Quality of Life
Tidsramme: 12 months.
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Efficacy will be measured using the EQ 5D Quality of Life assessment tool
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12 months.
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Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Timothy O Brien, PhD, NUIG
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Mohamed SA, Howard L, McInerney V, Hayat A, Krawczyk J, Naughton S, Finnerty A, Holohan M, Duffy A, Moloney T, Kavanagh E, Burke P, Liew A, Tubassam M, Walsh SR, O'Brien T. Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities. Cytotherapy. 2020 Jun;22(6):313-321. doi: 10.1016/j.jcyt.2020.02.007. Epub 2020 Apr 6.
- EU Clinical Trials Register Clinical trial results 2013-003447-37 version 1 EU-CTR publication date: of 21 01 January 2021
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 2013-001
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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