Intermittent ClaudicationPhase 2/3ABCNCT00539266
Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia
A Phase 2/3 study testing bone marrow derived mononuclear cells in people with Intermittent Claudication and Peripheral Vascular Diseases, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
The investigators propose confirm and extend the findings of open studies on the apparent efficacy of bone-marrow derived mononuclear cells for the induction of arteriogenesis in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Intermittent Claudication, Peripheral Vascular Diseases
- What is being tested?
- bone marrow derived mononuclear cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2007to Oct 2012
- Phase
- Phase 2/3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- persistent (>3 months) disabling claudication (Fontaine's stages IIb or Rutherford's categories 3, viz. pain free walking distance less than 100 meter) despite optimal therapy or critical limb ischemia (Fontaine's stages III/IV or Rutherford's categories 4-6)
- ineligibility for angioplasty or bypass procedures
- male of female, >18 years old
- life expectancy > 1 year
- written informed consent
Who cannot join
- candidates for angioplasty or bypass procedures
- inability to undergo bone marrow harvesting
- any condition in the affected limb that is anticipated to require surgical intervention in the first weeks after BM-MNC treatment
- life threatening co-morbidity
- poorly controlled diabetes (HbA1C > 10%)
- active malignancy in the 5 years prior to treatment
Show all 11Show fewer
- INR >1.5 at the time of bone-marrow harvest
- bleeding diathesis
- inability to undergo arterial catheterization
- inability to follow the protocol and to comply with the follow up requirements
- any other conditions that, in the opinion of the investigators, could interfere with the therapy or could pose a significant threat to the subject if the investigational therapy was to be initiated
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, 2300RC
Jan HN Lindeman, MD, PhD, #31 (0)71 5263968, Lindeman@lumc.nl
About this study
Official title: Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia A Double Blind, Placebo Controlled, Study in Diabetic and Non-diabetic Patients
The investigators propose confirm and extend the findings of open studies on the apparent efficacy of bone-marrow derived mononuclear cells for the induction of arteriogenesis in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.
Read the detailed description
Although the safety and beneficial effects of intramuscular transplantation of bone marrow derived mononuclear cells procedure appear well documented, a number of critical question regarding application of BM-MNC for peripheral vascular disease remain to be answered. First, although the original study has been partially performed as semi-blinded study (patients with double sided claudication were recruited and blindly treated with BM-MNC in one leg and peripheral blood injections in the other leg), this approach does exclude a placebo effect. Second, although patients with mild diabetes were included in the protocol, the results for diabetic patients were not analyzed separately. Diabetic disease is characterized by monocyte and endothelial progenitor cell dysfunction and it is still unclear whether this approach is also effective in diabetic patients. Third, although six-month results are reported long-term efficacy has not been established yet.
To address these issues, the investigators now propose confirm and extend the findings from open studies in a randomized double-blind study in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.
- Being tested
- bone marrow derived mononuclear cells, placebo
- Keywords
- Claudication, Critical limb ischemia, Cell therapy, Bone marrow
- Medical subject headings
- Intermittent Claudication, Peripheral Vascular Diseases, Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bone marrow derived mononuclear cellsBiological
40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
placeboBiological
40 IM injections (calf muscle) of placebo suspension
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | non diabetic patients with Fontaine IIb-IV peripheral artery disease Receives: Biological: bone marrow derived mononuclear cells |
| 2 | Placebo comparator | non diabetic patients with Fontaine IIb-IV peripheral artery disease Receives: Biological: placebo |
| 3 | Active comparator | diabetic patients with Fontaine IIb-IV peripheral artery disease Receives: Biological: bone marrow derived mononuclear cells |
| 4 | Placebo comparator | diabetic patients with Fontaine IIb-IV peripheral artery disease Receives: Biological: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Limb salvage/wound healing at t=6 months; Pain free walking distance
Measured: 6 months
Secondary outcomes (1)
quality of life (RAND-36), pain Scores (Brief Pain Inventory), tcO2 (wrist/ankle ratio) ABI Collateral artery scores (angiogram) at t=6 months, Limb salvage/wound healing at t= 3 and 12 months, Pain free walking distance at t=3 and 12 months,
Measured: 3, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionOct 2012 (estimated)
- Study completionOct 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intermittent ClaudicationStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Jan HN Lindeman, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00539266
- Sponsor's protocol ID
- P07.058
- Acronym
- ABC
- Status last verified
- Oct 2007
- First submitted
- 3 Oct 2007
- Last updated
- 6 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Moazzami B, Mohammadpour Z, Zabala ZE, Farokhi E, Roohi A, Dolmatova E, Moazzami K. Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD008347. doi: 10.1002/14651858.CD008347.pub4.
PubMed 35802393Lindeman JHN, Zwaginga JJ, Kallenberg-Lantrua G, van Wissen RC, Schepers A, van Bockel HJ, Fibbe WE, Hamming JF. No Clinical Benefit of Intramuscular Delivery of Bone Marrow-derived Mononuclear Cells in Nonreconstructable Peripheral Arterial Disease: Results of a Phase-III Randomized-controlled Trial. Ann Surg. 2018 Nov;268(5):756-761. doi: 10.1097/SLA.0000000000002896.
PubMed 30004916
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia A Double Blind, Placebo Controlled, Study in Diabetic and Non-diabetic Patients
- ClinicalTrials.gov ID
- NCT00539266
- Acronym / sponsor ID
- ABC / P07.058
- Keywords
- Claudication, Critical limb ischemia, Cell therapy, Bone marrow
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Oct 2012 (estimated)
- Study completion
- Oct 2012 (estimated)
- First posted
- 4 Oct 2007 (estimated)
- 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.
The investigators propose confirm and extend the findings of open studies on the apparent efficacy of bone-marrow derived mononuclear cells for the induction of arteriogenesis in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.
Detailed description
Although the safety and beneficial effects of intramuscular transplantation of bone marrow derived mononuclear cells procedure appear well documented, a number of critical question regarding application of BM-MNC for peripheral vascular disease remain to be answered. First, although the original study has been partially performed as semi-blinded study (patients with double sided claudication were recruited and blindly treated with BM-MNC in one leg and peripheral blood injections in the other leg), this approach does exclude a placebo effect. Second, although patients with mild diabetes were included in the protocol, the results for diabetic patients were not analyzed separately. Diabetic disease is characterized by monocyte and endothelial progenitor cell dysfunction and it is still unclear whether this approach is also effective in diabetic patients. Third, although six-month results are reported long-term efficacy has not been established yet.
To address these issues, the investigators now propose confirm and extend the findings from open studies in a randomized double-blind study in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Biological: bone marrow derived mononuclear cellsnon diabetic patients with Fontaine IIb-IV peripheral artery disease |
| 2 | Placebo comparator | Biological: placebonon diabetic patients with Fontaine IIb-IV peripheral artery disease |
| 3 | Active comparator | Biological: bone marrow derived mononuclear cellsdiabetic patients with Fontaine IIb-IV peripheral artery disease |
| 4 | Placebo comparator | Biological: placebodiabetic patients with Fontaine IIb-IV peripheral artery disease |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- persistent (>3 months) disabling claudication (Fontaine's stages IIb or Rutherford's categories 3, viz. pain free walking distance less than 100 meter) despite optimal therapy or critical limb ischemia (Fontaine's stages III/IV or Rutherford's categories 4-6)
- ineligibility for angioplasty or bypass procedures
- male of female, >18 years old
- life expectancy > 1 year
- written informed consent
Key exclusion criteria (11 listed)
- candidates for angioplasty or bypass procedures
- inability to undergo bone marrow harvesting
- any condition in the affected limb that is anticipated to require surgical intervention in the first weeks after BM-MNC treatment
- life threatening co-morbidity
- poorly controlled diabetes (HbA1C > 10%)
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 |
|---|---|---|
| bone marrow derived mononuclear cells40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells | Biological | 1, 3 |
| placebo40 IM injections (calf muscle) of placebo suspension | Biological | 2, 4 |
Primary outcome
Limb salvage/wound healing at t=6 months; Pain free walking distance
Time frame: 6 months
1 secondary outcome
quality of life (RAND-36), pain Scores (Brief Pain Inventory), tcO2 (wrist/ankle ratio) ABI Collateral artery scores (angiogram) at t=6 months, Limb salvage/wound healing at t= 3 and 12 months, Pain free walking distance at t=3 and 12 months,
Time frame: 3, 6 and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2011.
- Derived from this study: PubMed 35802393Moazzami B, Mohammadpour Z, Zabala ZE, Farokhi E, Roohi A, Dolmatova E, Moazzami K. Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD008347. doi: 10.1002/14651858.CD008347.pub4.
- Derived from this study: PubMed 30004916Lindeman JHN, Zwaginga JJ, Kallenberg-Lantrua G, van Wissen RC, Schepers A, van Bockel HJ, Fibbe WE, Hamming JF. No Clinical Benefit of Intramuscular Delivery of Bone Marrow-derived Mononuclear Cells in Nonreconstructable Peripheral Arterial Disease: Results of a Phase-III Randomized-controlled Trial. Ann Surg. 2018 Nov;268(5):756-761. doi: 10.1097/SLA.0000000000002896.
Related trials for Intermittent Claudication
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
RecruitingPhase 3
Improving Mobility After Revascularization in Peripheral Artery Disease
Peripheral Artery Disease, Intermittent Claudication
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.
Jan HN Lindeman, MD, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing bone marrow derived mononuclear cells in people with Intermittent Claudication and Peripheral Vascular Diseases, run by Leiden University Medical Center at 1 site in Netherlands.
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 5 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 6 Jul 2011. 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 Netherlands. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jan HN Lindeman, MD, PhD (#31 (0)71 5263968, Lindeman@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Limb salvage/wound healing at t=6 months; Pain free walking distance (time frame: 6 months). 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 NCT00539266, which also lists 2 linked publications.
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 6 Jul 2011.