Transfemoral AmputationMMPOPNCT02564432
Microbiome and Metagenome in Percutaneous Osseointegrated Prostheses (MMPOP)
An observational study of Transfemoral Amputation, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The purpose of this study is to investigate the clinical implementation of a new percutaneous prosthetic attachment system by determining the resident microbial ecology of the implant exit site and to simultaneously study the systemic and local stomal immune responses. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Transfemoral Amputation
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2015to 30 Sep 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 10 transfemoral amputees selected from Veteran and active military populations
Who may be able to join
- Is a US military Veteran with transfemoral limb loss, that occurred at least 6 months prior to consent, and that the amputation is not a result of dysvascular disease.
- Is at least 18 years of age or older.
- Has previously used or is currently using a "socket suspension technology" prosthesis
- Has, in the opinion of the investigator, normal cognitive function and no physical limitations, addictive diseases, or underlying medical conditions including tobacco use (continued testing for tobacco use will be performed at screening) that may prevent the subject from being an appropriate study candidate.
- Is willing, able, and committed to participation in baseline and follow-up evaluations for the entire duration of the study.
- Can provide written informed consent to participate.
Who cannot join
- Is currently on active or reserve military duty
- Has experienced systemic bacterial infection or localized infection at the stump site within the previous 6 months
- Has had more than 1 limb amputated
- Has a body mass index (BMI) 30
- Has insulin dependent diabetes mellitus (IDDM) or has adult onset DM with a glycated hemoglobin (HbA1c) > 53 mmol/mol (7.0%) at screening
- Has residual femur bone length of less than 25% of the length of the contralateral femur.
Show all 14Show fewer
- Has clinically diagnosed vascular compromise proximal to the surgical site
- Is pregnant at the time of surgery or plans to become pregnant within the first year of follow-up
- Has evidence of recent tobacco use (urine cotinine test > 300 ng/mL [1703 nmol/L]) and is not committed to a smoking-cessation program
- Has renal insufficiency (defined as serum creatinine of 1.8 mg/dL) or is currently receiving renal dialysis
- Is currently involved in or plans to be involved in high levels of physical activity (competitive sports, heavy physical labor, etc) during the first 12 months of the rehabilitation stage
- Has muscular, neurologic or vascular deficiencies that may compromise the bone or soft tissue healing of the affected extremity
- Has anemia characterized by a hemoglobin of 11 g/dL at the time of surgery
- Is currently on oral anticoagulation (excluding low-dose aspirin for cardiac prophylaxis)
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148
About this study
Official title: Microbiome and Innate Immunity With Percutaneous Osseointegrated Prostheses
The purpose of this study is to investigate the clinical implementation of a new percutaneous prosthetic attachment system by determining the resident microbial ecology of the implant exit site and to simultaneously study the systemic and local stomal immune responses. This study will follow 10 patients implanted with percutaneous osseointegrated prosthetics (POPs) for a period of one year. Two state-of-the-art, pre- and post-surgery bacterial monitoring technologies will be used; these procedures are intended to facilitate the early prediction, detection, and treatment of infection, as well as to provide follow-up data that can potentially be used to advantageously manipulate the stomal microbial environment in future clinical trials.
Commensal skin bacteria colonize all stomas. Colonization does not necessarily result in infection. Over time, the presence of this skin penetrating foreign object (implant) will cause measurable changes in the bacterial population (microbiota) at and around the POP exit site. It is anticipated that the evolving microbiota, in concert with measurable changes in the local and systemic cytokine responses, will reveal patterns associated with mutualistic-commensal bacteria and/or pathogenic bacteria related to the stages of chronic wound healing. These patterns could be used to determine the presence of a stable uninfected stoma or the progression of a stomal infection. Hopefully, this information will allow timely intervention to prevent infection, i.e. by detecting early stages of infection or discerning common patterns of stable mutualistic-commensal bacterial strains, effective intervention protocols (antibiotics, probiotics or manipulation of the stomal and skin microbiota) may be developed to avoid patient morbidity and assure implant survival.
Read the detailed description
Percutaneous osseointegrated prosthetic (POP) attachment (i.e., the direct skeletal attachment of artificial limbs) is a rapidly evolving technology. This follows over a decade of successful European trials that largely involved transfemoral amputees. This information together with the translational animal studies have made it possible to commence an Early Feasibility Device Exemption (IDE) Pilot Program under the direction of the Federal Drug Administration (FDA). Ten transfemoral amputees, selected from the Veteran and active military populations will receive a novel POP device. The objective of this study is to follow 10 patients implanted with a POP for a period of one year.
All stomas are colonized by local skin bacteria; colonization does not necessarily result in infection. Over time, the presence of this skin penetrating foreign object (implant) will cause measurable changes in the bacterial population (microbiota) at and around the POP exit site.
It is anticipated that the evolving microbiota, in concert with measurable changes in the local and systemic cytokine responses, will reveal patterns associated with mutualistic-commensal bacteria and/or pathogenic bacteria related to the stages of chronic wound healing. These patterns could be used to determine the presence of a stable uninfected stoma or the progression of a stomal infection. Hopefully, this information will allow timely intervention to prevent infection, i.e. by detecting early stages of infection or discerning common patterns of stable mutualistic-commensal bacterial strains, effective intervention protocols (antibiotics, probiotics or manipulation of the stomal and skin microbiota) may be developed to avoid patient morbidity and assure implant survival.
The study aims will test the following:
Aim 1: Determine and characterize the microbiota in the region surrounding the skin/implant interface. Sampling will take place over all stages of wound healing and stomal maturation and will begin with Stage 1 and Stage 2 surgeries, as well as at defined time points, and collection sites (i.e., the stoma, ipsilateral and contralateral thigh skin) for up to one year post surgery. This will be carried-out by using a specific swabbing technique to collect bacterial and fungal deoxyribonucleic acid (DNA) and to amplify and sequence bacterial 16 Svedberg units ribosomal ribonucleic acid (16S rRNA) and fungal 18 Svedberg units ribosomal ribonucleic acid (18S rRNA) genes.
AIM 2: Compare the expression patterns of the local and systemic inflammatory biomarkers over time and determine if there is a correlation with the microbiota pattern to diagnose the state of wound healing at the skin/implant interface and the systemic response to a potentially life-long chronic wound. The measurements of the pro-inflammatory cytokines, found in the stomal exudate (local biomarkers) and blood serum (systemic biomarkers), along with evolving microbiota profiles (Aim #1) will help to better characterize the homeostatic state of the stoma and subsequent optimum wound care therapies.
The ability to predict infection and to avoid it without the use of antibiotics would be of great value to future clinical trials. Assuming the success of this feasibility pilot trial, it is anticipated that the trial will be expanded to include 200 patients.
- Conditions
- Transfemoral Amputation
- Keywords
- amputee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| POP 10 patient cohort | This is an observational study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bacterial Community Types as Determined by Percentage RNA Sequence Reads
To compare, within each participant, the Bacterial Community Type dynamics over time, we used Loess regression to visualize local (temporal) trends in the data. Specifically, it takes the scatter-plot of values (relative abundances, diversity indices) and uses smoothing to identify local trends in the data. As percentage RNA sequence reads were the measure of central tendency, measure of dispersion of the data was not possible to calculate.
Measured: On Day 3 after first surgery and day 3 prior to and days, 3, 14 and week 6 and months 3, 6, 9 and 12 after second surgery.
Secondary outcomes (1)
Time to Equilibrium of the Bacterial Community Types Over the Duration of the Study
Times required to reach stable Bacterial Community Types (CT) after the Stage 2 surgery. Dirichlet multinomial mixture modeling was used to examine the heterogeneity and optimal number of the community compositions within each sample site. Often, skin samples clustered optimally to a single community type. Five community types (CT1-5) were identified: CT1 was defined by mixed communities of obligate anaerobes. CT2 was defined as those with median Shannon diversity index of ~4.5. CT3 was defined as the microbial community with the Shannon index of ~ 0.6 and dominated by Streptococcus. CT4 and CT5 were characterized by high relative abundances of Corynebacterium (median = 49%) and Staphylococcus (median = 34%), respectively. Patients, post-surgery, stabilized to one of CT1 - CT5 stomal microbiota.
Measured: On Day 3 after first surgery and day 3 prior to and days, 3, 14 and week 6 and months 3, 6, 9 and 12 after second surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2015 (estimated)
- Study start1 Oct 2015
- Primary completion18 Apr 2018
- Study completion30 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Transfemoral AmputationStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- James P Beck, MD, Principal investigator, VA Salt Lake City Health Care System, Salt Lake City, UT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02564432
- Sponsor's protocol ID
- A1544-I
- Acronym
- MMPOP
- Status last verified
- Feb 2020
- First submitted
- 29 Sep 2015
- Last updated
- 19 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microbiome and Innate Immunity With Percutaneous Osseointegrated Prostheses
- ClinicalTrials.gov ID
- NCT02564432
- Acronym / sponsor ID
- MMPOP / A1544-I
- Conditions
- Transfemoral Amputation
- Keywords
- amputee
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 18 Apr 2018 (actual)
- Study completion
- 30 Sep 2018 (actual)
- First posted
- 30 Sep 2015 (estimated)
- Results
- Posted 19 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the clinical implementation of a new percutaneous prosthetic attachment system by determining the resident microbial ecology of the implant exit site and to simultaneously study the systemic and local stomal immune responses. This study will follow 10 patients implanted with percutaneous osseointegrated prosthetics (POPs) for a period of one year. Two state-of-the-art, pre- and post-surgery bacterial monitoring technologies will be used; these procedures are intended to facilitate the early prediction, detection, and treatment of infection, as well as to provide follow-up data that can potentially be used to advantageously manipulate the stomal microbial environment in future clinical trials.
Commensal skin bacteria colonize all stomas. Colonization does not necessarily result in infection. Over time, the presence of this skin penetrating foreign object (implant) will cause measurable changes in the bacterial population (microbiota) at and around the POP exit site. It is anticipated that the evolving microbiota, in concert with measurable changes in the local and systemic cytokine responses, will reveal patterns associated with mutualistic-commensal bacteria and/or pathogenic bacteria related to the stages of chronic wound healing. These patterns could be used to determine the presence of a stable uninfected stoma or the progression of a stomal infection. Hopefully, this information will allow timely intervention to prevent infection, i.e. by detecting early stages of infection or discerning common patterns of stable mutualistic-commensal bacterial strains, effective intervention protocols (antibiotics, probiotics or manipulation of the stomal and skin microbiota) may be developed to avoid patient morbidity and assure implant survival.
Detailed description
Percutaneous osseointegrated prosthetic (POP) attachment (i.e., the direct skeletal attachment of artificial limbs) is a rapidly evolving technology. This follows over a decade of successful European trials that largely involved transfemoral amputees. This information together with the translational animal studies have made it possible to commence an Early Feasibility Device Exemption (IDE) Pilot Program under the direction of the Federal Drug Administration (FDA). Ten transfemoral amputees, selected from the Veteran and active military populations will receive a novel POP device. The objective of this study is to follow 10 patients implanted with a POP for a period of one year.
All stomas are colonized by local skin bacteria; colonization does not necessarily result in infection. Over time, the presence of this skin penetrating foreign object (implant) will cause measurable changes in the bacterial population (microbiota) at and around the POP exit site.
It is anticipated that the evolving microbiota, in concert with measurable changes in the local and systemic cytokine responses, will reveal patterns associated with mutualistic-commensal bacteria and/or pathogenic bacteria related to the stages of chronic wound healing. These patterns could be used to determine the presence of a stable uninfected stoma or the progression of a stomal infection. Hopefully, this information will allow timely intervention to prevent infection, i.e. by detecting early stages of infection or discerning common patterns of stable mutualistic-commensal bacterial strains, effective intervention protocols (antibiotics, probiotics or manipulation of the stomal and skin microbiota) may be developed to avoid patient morbidity and assure implant survival.
The study aims will test the following:
Aim 1: Determine and characterize the microbiota in the region surrounding the skin/implant interface. Sampling will take place over all stages of wound healing and stomal maturation and will begin with Stage 1 and Stage 2 surgeries, as well as at defined time points, and collection sites (i.e., the stoma, ipsilateral and contralateral thigh skin) for up to one year post surgery. This will be carried-out by using a specific swabbing technique to collect bacterial and fungal deoxyribonucleic acid (DNA) and to amplify and sequence bacterial 16 Svedberg units ribosomal ribonucleic acid (16S rRNA) and fungal 18 Svedberg units ribosomal ribonucleic acid (18S rRNA) genes.
AIM 2: Compare the expression patterns of the local and systemic inflammatory biomarkers over time and determine if there is a correlation with the microbiota pattern to diagnose the state of wound healing at the skin/implant interface and the systemic response to a potentially life-long chronic wound. The measurements of the pro-inflammatory cytokines, found in the stomal exudate (local biomarkers) and blood serum (systemic biomarkers), along with evolving microbiota profiles (Aim #1) will help to better characterize the homeostatic state of the stoma and subsequent optimum wound care therapies.
The ability to predict infection and to avoid it without the use of antibiotics would be of great value to future clinical trials. Assuming the success of this feasibility pilot trial, it is anticipated that the trial will be expanded to include 200 patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| POP 10 patient cohort | – | –This is an observational study |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 10 transfemoral amputees selected from Veteran and active military populations
Key inclusion criteria (6 listed)
- Is a US military Veteran with transfemoral limb loss, that occurred at least 6 months prior to consent, and that the amputation is not a result of dysvascular disease.
- Is at least 18 years of age or older.
- Has previously used or is currently using a "socket suspension technology" prosthesis
- Has, in the opinion of the investigator, normal cognitive function and no physical limitations, addictive diseases, or underlying medical conditions including tobacco use (continued testing for tobacco use will be performed at screening) that may prevent the subject from being an appropriate study candidate.
- Is willing, able, and committed to participation in baseline and follow-up evaluations for the entire duration of the study.
Key exclusion criteria (14 listed)
- Is currently on active or reserve military duty
- Has experienced systemic bacterial infection or localized infection at the stump site within the previous 6 months
- Has had more than 1 limb amputated
- Has a body mass index (BMI) 30
- Has insulin dependent diabetes mellitus (IDDM) or has adult onset DM with a glycated hemoglobin (HbA1c) > 53 mmol/mol (7.0%) at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Bacterial Community Types as Determined by Percentage RNA Sequence Reads
Time frame: On Day 3 after first surgery and day 3 prior to and days, 3, 14 and week 6 and months 3, 6, 9 and 12 after second surgery.
To compare, within each participant, the Bacterial Community Type dynamics over time, we used Loess regression to visualize local (temporal) trends in the data. Specifically, it takes the scatter-plot of values (relative abundances, diversity indices) and uses smoothing to identify local trends in the data. As percentage RNA sequence reads were the measure of central tendency, measure of dispersion of the data was not possible to calculate.
1 secondary outcome
Time to Equilibrium of the Bacterial Community Types Over the Duration of the Study
Time frame: On Day 3 after first surgery and day 3 prior to and days, 3, 14 and week 6 and months 3, 6, 9 and 12 after second surgery.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
James P Beck, MD principal investigator
VA Salt Lake City Health Care System, Salt Lake City, UT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transfemoral Amputation, run by VA Office of Research and Development at 1 site in United States.
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 6 inclusion and 14 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: finished, as of the sponsor's last update on 19 Feb 2020. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Bacterial Community Types as Determined by Percentage RNA Sequence Reads (time frame: On Day 3 after first surgery and day 3 prior to and days, 3, 14 and week 6 and months 3, 6, 9 and 12 after second surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Feb 2020.