TraumaNCT04976049
Use of 5-Aminolevulinic Acid to Assess Bone and Tissue Profusion in Orthopaedic Infection Patients
An observational study of Trauma and Infection, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
The focus of this study is to explore the variability distribution of 5-Aminolevulinic Acid (ALA)associated with bone and soft tissue perfusion in infection patients, using 5-ALA fluorescence imaging. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Trauma, Infection, Bone Fracture
- What is being tested?
- Imaging using 5-Aminolevulinic Acid (5-ALA) during surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Aug 2021to 21 Nov 2022
- Phase
- Observational
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients 18 years of age or older who present to Dartmouth-Hitchcock Medical Center with an orthopaedic infection
Who may be able to join
- Patients 18 years of age or older.
- History of an extremity fracture.
- Prior definitive fracture management with external fixation, internal fixation, or joint fusion.
- Superficial, deep, or organ space surgical site infection (SSI) (as per Center for Disease Control criteria) at the fracture site that requires operative management.
- Will have all planned SSI care surgeries performed by a participating surgeon or delegate.
- Provision of informed consent.
Who cannot join
- Fractures of the hand cannot be imaged.
- Iodine allergy.
- Burns at the SSI site.
- Incarceration.
- Expected survival of less than 90 days.
- Problems, in the judgment of study personnel, with maintaining follow-up with the patient.
Show all 14Show fewer
- Adults unable to consent or whom do not have a legal authorized representative
- Individuals who are not yet adults (infants, children, teenagers)
- Pregnant or breastfeeding women
- History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis.
- History of liver disease within the last 12 months.
- Elevated liver function tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase or bilirubin levels greater than 2.5 times the normal limit) from laboratory tests conducted within 30 days prior to surgery.
- Serum creatinine in excess of 180 µmol/L within 30 days prior to surgery.
- Inability to comply with the photosensitivity precautions associated with the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
The focus of this study is to explore the variability distribution of 5-Aminolevulinic Acid (ALA)associated with bone and soft tissue perfusion in infection patients, using 5-ALA fluorescence imaging. In additional this study plans to evaluate the change in 5-ALA distribution from pre to post debridement and to preliminarily determine whether an orally administered dose of 20mg/kg 5-ALA can predict recurrent infection/treatment failure.
Read the detailed description
The focus of this study is to (1) Explore variability in distribution of 5-Aminolevulinic Acid (ALA) in bone and soft tissue infection (2) Evaluate the change in 5-ALA distribution from pre to post debridement (3) Preliminarily determine whether 5-ALA has the possibility predict infection / treatment failure
Infection following trauma is one of the most prevalent and challenging complications faced by orthopedic surgeons in both military and civilian populations, occurring after up to 60% of open bone fractures. Several factors specific to this trauma place patients at high risk for infectious complications, including: traumatized tissues, open contaminated fracture, soft tissue coverage issues, catabolic state due to poly-trauma, prolonged hospitalization with exposure to nosocomial bacteria, and presence of metallic implants8. Infection requires one or more unplanned surgical procedures and leads to prolonged morbidity, loss of function, and potential loss of limb1. Failed treatment for bone infection results in recurrent infection, requiring repeat surgical procedures in approximately 30% of patients.
Studies are currently being conducted to evaluate the utility of first window Indocyanine Green (ICG) to identify areas of deficient perfusion. This is based upon the concept deficient perfusion prevents delivery of antibiotics and endogenous immune cells to traumatized tissues. In the setting of established infection, poorly perfused bone can be a nidus for biofilm formation creating resistance to antibiotics. However, in the context of this work it is becoming increasingly clear that acute (rather than chronic) infections display hyper vascularity with increased blood flow and neovascularization. Infection is known to display the enhanced permeability and retention effect with increased vascular permeability.
There are currently no accepted intraoperative tools that can be used to make objective decisions about which bone and tissue is infected and which is normal. Methods currently used to guide debridement are quite rudimentary. Clinical judgement is based on the gross appearance of soft tissue and bone, including color, turgor, and extent of soft tissue stripping. A burr may be used to look for bleeding bone. More extensive debridement is thought to minimize risk of index infection or reduce the rate of persistent infection; however, this comes at the cost of increasingly complex reconstructive procedures to fill bony defects. Clearly what is needed is a functional imaging system which can identify infected tissues to guide surgeons in the amount of tissue to debride. In turn, this will lead to fewer infections and a more effective treatment of surgical site infections (SSIs) at the fracture site. Both scenarios will allow patients to return to duty or work sooner.
- Conditions
- Trauma, Infection, Bone Fracture
- Being tested
- Imaging using 5-Aminolevulinic Acid (5-ALA) during surgery
- Keywords
- 5-Aminolevulinic Acid, infection, orthopedics, imaging
- Medical subject headings
- Wounds and Injuries, Infections, Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imaging using 5-Aminolevulinic Acid (5-ALA) during surgeryProcedure or surgery
Patients will be administered FDA approved oral 5-ALA and imaged by a FDA approved surgical fluorescence imaging device (Spy Elite) which is 0.5 meter away from the subject.
| Study group | Role | What they receive |
|---|---|---|
| Orthopedic infection | Subjects who have undergone previous trauma surgeries and have developed an infection will be assessed for protocol inclusion criteria. Patients will be administered a single, oral, 20mg/kg dose of 5-Aminolevulinic Acid (ALA) by a qualified member of their care team. This dose will be administered ideally 3 hours prior to surgery. Fluorescent imaging will be obtained pre and post irrigation and debridement. Receives: Procedure: Imaging using 5-Aminolevulinic Acid (5-ALA) during surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
5-Aminolevulinic Acid distribution variability
Distribution of 5-Aminolevulinic Acid in the bone and soft tissue of infection patients, measured using fluorescent imaging.
Measured: One Day
Secondary outcomes (1)
5-Aminolevulinic Acid distribution pre and post debridement.
Distribution of 5-Aminolevulinic Acid in bone and soft tissue prior to and following debridement, measure using fluorescent imaging
Measured: One Day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2021
- Study start13 Aug 2021
- Primary completion30 Aug 2022 (estimated)
- Study completion21 Nov 2022
Why it stopped: Principle Investigator decided not to pursue study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TraumaStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ida Leah Gitajn, Dartmouth-Hitchcock Medical Center
- Investigators
- Ida L Gitajn, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04976049
- Sponsor's protocol ID
- STUDY02000990
- Status last verified
- Nov 2022
- First submitted
- 2 Jun 2021
- Last updated
- 28 Nov 2022
- Results posted
- No
- 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 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of 5-Aminolevulinic Acid to Assess Bone and Tissue Profusion in Orthopaedic Infection Patients
- ClinicalTrials.gov ID
- NCT04976049
- Acronym / sponsor ID
- STUDY02000990
- Conditions
- Trauma, Infection, Bone Fracture
- Keywords
- 5-Aminolevulinic Acid, infection, orthopedics, imaging
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Principle Investigator decided not to pursue study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- 13 Aug 2021 (actual)
- Primary completion
- 30 Aug 2022 (estimated)
- Study completion
- 21 Nov 2022 (actual)
- First posted
- 26 Jul 2021 (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.
The focus of this study is to explore the variability distribution of 5-Aminolevulinic Acid (ALA)associated with bone and soft tissue perfusion in infection patients, using 5-ALA fluorescence imaging. In additional this study plans to evaluate the change in 5-ALA distribution from pre to post debridement and to preliminarily determine whether an orally administered dose of 20mg/kg 5-ALA can predict recurrent infection/treatment failure.
Detailed description
The focus of this study is to (1) Explore variability in distribution of 5-Aminolevulinic Acid (ALA) in bone and soft tissue infection (2) Evaluate the change in 5-ALA distribution from pre to post debridement (3) Preliminarily determine whether 5-ALA has the possibility predict infection / treatment failure
Infection following trauma is one of the most prevalent and challenging complications faced by orthopedic surgeons in both military and civilian populations, occurring after up to 60% of open bone fractures. Several factors specific to this trauma place patients at high risk for infectious complications, including: traumatized tissues, open contaminated fracture, soft tissue coverage issues, catabolic state due to poly-trauma, prolonged hospitalization with exposure to nosocomial bacteria, and presence of metallic implants8. Infection requires one or more unplanned surgical procedures and leads to prolonged morbidity, loss of function, and potential loss of limb1. Failed treatment for bone infection results in recurrent infection, requiring repeat surgical procedures in approximately 30% of patients.
Studies are currently being conducted to evaluate the utility of first window Indocyanine Green (ICG) to identify areas of deficient perfusion. This is based upon the concept deficient perfusion prevents delivery of antibiotics and endogenous immune cells to traumatized tissues. In the setting of established infection, poorly perfused bone can be a nidus for biofilm formation creating resistance to antibiotics. However, in the context of this work it is becoming increasingly clear that acute (rather than chronic) infections display hyper vascularity with increased blood flow and neovascularization. Infection is known to display the enhanced permeability and retention effect with increased vascular permeability.
There are currently no accepted intraoperative tools that can be used to make objective decisions about which bone and tissue is infected and which is normal. Methods currently used to guide debridement are quite rudimentary. Clinical judgement is based on the gross appearance of soft tissue and bone, including color, turgor, and extent of soft tissue stripping. A burr may be used to look for bleeding bone. More extensive debridement is thought to minimize risk of index infection or reduce the rate of persistent infection; however, this comes at the cost of increasingly complex reconstructive procedures to fill bony defects. Clearly what is needed is a functional imaging system which can identify infected tissues to guide surgeons in the amount of tissue to debride. In turn, this will lead to fewer infections and a more effective treatment of surgical site infections (SSIs) at the fracture site. Both scenarios will allow patients to return to duty or work sooner.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Orthopedic infection | – | Procedure: Imaging using 5-Aminolevulinic Acid (5-ALA) during surgerySubjects who have undergone previous trauma surgeries and have developed an infection will be assessed for protocol inclusion criteria. Patients will be administered a single, oral, 20mg/kg dose of 5-Aminolevulinic Acid (ALA) by a qualified member of their care team. This dose will be administered ideally 3 hours prior to surgery. Fluorescent imaging will be obtained pre and post irrigation and debridement. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients 18 years of age or older who present to Dartmouth-Hitchcock Medical Center with an orthopaedic infection
Key inclusion criteria (6 listed)
- Patients 18 years of age or older.
- History of an extremity fracture.
- Prior definitive fracture management with external fixation, internal fixation, or joint fusion.
- Superficial, deep, or organ space surgical site infection (SSI) (as per Center for Disease Control criteria) at the fracture site that requires operative management.
- Will have all planned SSI care surgeries performed by a participating surgeon or delegate.
Key exclusion criteria (14 listed)
- Fractures of the hand cannot be imaged.
- Iodine allergy.
- Burns at the SSI site.
- Incarceration.
- Expected survival of less than 90 days.
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 |
|---|---|---|
| Imaging using 5-Aminolevulinic Acid (5-ALA) during surgeryPatients will be administered FDA approved oral 5-ALA and imaged by a FDA approved surgical fluorescence imaging device (Spy Elite) which is 0.5 meter away from the subject. | Procedure or surgery | Orthopedic infection |
Primary outcome
5-Aminolevulinic Acid distribution variability
Time frame: One Day
Distribution of 5-Aminolevulinic Acid in the bone and soft tissue of infection patients, measured using fluorescent imaging.
1 secondary outcome
5-Aminolevulinic Acid distribution pre and post debridement.
Time frame: One Day
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2022.
- 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.
Ida L Gitajn principal investigator
Dartmouth-Hitchcock Medical Center
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 Trauma and Infection, run by Dartmouth-Hitchcock Medical Center 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: withdrawn, as of the sponsor's last update on 28 Nov 2022. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
5-Aminolevulinic Acid distribution variability (time frame: One Day). 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 28 Nov 2022.