Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities

NCT02240498 | Completed Phase 1

• 1 other identifier: RSRB00049677
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this Phase 1 study are to evaluate the safety and feasibility of methylene-blue-mediated photodynamic therapy (MB-PDT) performed at the time of abscess drainage to treat deep tissue abscesses. Safety will be evaluated by physical examination and imaging and laboratory studies in order to identify adverse events that may be induced by MB-PDT. We hypothesize that MB-PDT will be a safe and feasible intervention for this patient population. Optical measurements will additionally be performed at the abscess wall to determine optical properties and methylene blue uptake.

Conditions

Abscess

Keywords

Abscess; Drainage

Outcome Measures

Primary Outcomes (7)

• Number of study-related serious adverse events

  Up to 14 days post-procedure

• Number of patients with study-related unanticipated adverse events

  Up to 14 days post-procedure

• Evidence of fat embolism

  Presentation of symptoms, including tachycardia, tachypnea, respiratory failure, decline in hematocrit, thrombocytopenia, and alteration of mental status in patient, will be deemed an unsafe outcome

  Within 4 hours of Intralipid administration

• Methylene blue escape during procedure with evidence of adverse reaction

  If greater than 3 mg/kg of methylene blue escapes from the abscess (i.e. is not recovered), subject will be placed under observation for 4 hours. During this time, methylene blue related adverse reactions will be assessed. Presence of any of these adverse reactions during the observation period will be considered a safety failure.

  Within 4 hours of methylene blue administration

• Disruption of the abscess wall and damage to surrounding tissue

  CT imaging post-procedure will be compared to pre-drainage CT imaging for evidence of disruption of the abscess wall and damage to surrounding tissue

  Up to 14 days post-procedure

• Need for surgery to remove a broken optical fiber fragment

  If an optical fiber breaks within the patient and surgery is required to retrieve the fragment, this will be deemed an unsafe outcome

  Within 1 hour of the study procedure

• Number of patients with technically successful procedure

  Technical success includes successful image-guided placement of drainage catheter into the abscess, administration of methylene blue and Intralipid, placement of the optical fiber, laser irradiation, and successful removal of the entire optical fiber

  Within one hour of the trial procedure

Study Arms (6)

MB-PDT, 5 min illumination

EXPERIMENTAL

Each subject in this group will receive methylene blue, 20% I.V. fat emulsion, insertion of optical fiber, and laser illumination, 5 minutes.

Drug: Methylene Blue; Drug: 20% I.V. Fat Emulsion; Device: Insertion of optical fiber; Device: Laser illumination, 5 minutes

MB-PDT, 10 min illumination

EXPERIMENTAL

Each subject in this group will receive methylene blue, 20% I.V. fat emulsion, insertion of optical fiber, optical spectroscopy measurement, and laser illumination, 10 minutes.

Drug: Methylene Blue; Drug: 20% I.V. Fat Emulsion; Device: Insertion of optical fiber; Device: Laser illumination, 10 minutes; Device: Optical spectroscopy measurement

MB-PDT, 15 min illumination

EXPERIMENTAL

Each subject in this group will receive methylene blue, 20% I.V. fat emulsion, insertion of optical fiber, optical spectroscopy measurement, and laser illumination, 15 minutes.

Drug: Methylene Blue; Drug: 20% I.V. Fat Emulsion; Device: Insertion of optical fiber; Device: Laser illumination, 15 minutes; Device: Optical spectroscopy measurement

MB-PDT, 20 min illumination

EXPERIMENTAL

Each subject in this group will receive methylene blue, 20% I.V. fat emulsion, insertion of optical fiber, optical spectroscopy measurement, and laser illumination, 20 minutes.

Drug: Methylene Blue; Drug: 20% I.V. Fat Emulsion; Device: Insertion of optical fiber; Device: Laser illumination, 20 minutes; Device: Optical spectroscopy measurement

MB-PDT, 25 min illumination

EXPERIMENTAL

Each subject in this group will receive methylene blue, 20% I.V. fat emulsion, insertion of optical fiber, optical spectroscopy measurement, and laser illumination, 25 minutes.

Drug: Methylene Blue; Drug: 20% I.V. Fat Emulsion; Device: Insertion of optical fiber; Device: Laser illumination, 25 minutes; Device: Optical spectroscopy measurement

MB-PDT, 30 min illumination

EXPERIMENTAL

Each subject in this group will receive methylene blue, 20% I.V. fat emulsion, insertion of optical fiber, optical spectroscopy measurement, and laser illumination, 30 minutes.

Drug: Methylene Blue; Drug: 20% I.V. Fat Emulsion; Device: Insertion of optical fiber; Device: Laser illumination, 30 minutes; Device: Optical spectroscopy measurement

Interventions

Methylene Blue DRUG

Administration of 1 mg/mL methylene blue to the abscess cavity, followed by a 10 minute incubation interval. After this incubation interval, the methylene blue solution will be aspirated from the cavity and flushed twice with sterile saline.

Also known as: Methylene Blue Injection, USP 1%

MB-PDT, 10 min illumination; MB-PDT, 15 min illumination; MB-PDT, 20 min illumination; MB-PDT, 25 min illumination; MB-PDT, 30 min illumination; MB-PDT, 5 min illumination

20% I.V. Fat Emulsion DRUG

The abscess cavity will be filled with sterile 1% Intralipid solution to gently distend the cavity and, through efficient light scattering, to homogenize the light dose to the walls of the cavity. After laser illumination, the Intralipid will be aspirated from the cavity.

Also known as: Intralipid 20%

MB-PDT, 10 min illumination; MB-PDT, 15 min illumination; MB-PDT, 20 min illumination; MB-PDT, 25 min illumination; MB-PDT, 30 min illumination; MB-PDT, 5 min illumination

Insertion of optical fiber DEVICE

A sterile, FDA-approved optical fiber will be advanced to the approximate center of the abscess cavity via the drainage catheter under image guidance. Following laser illumination, the fiber will be withdrawn.

Also known as: Vascular Solutions VariLase Bright Tip Fiber M7106

MB-PDT, 10 min illumination; MB-PDT, 15 min illumination; MB-PDT, 20 min illumination; MB-PDT, 25 min illumination; MB-PDT, 30 min illumination; MB-PDT, 5 min illumination

Laser illumination, 5 minutes DEVICE

Laser illumination will be delivered via the optical fiber for a duration of 5 minutes. The fluence rate will be set such that the maximum fluence rate at the abscess wall is 20 mW/cm2.

Also known as: Modulight ML7710-PDT Laser System

MB-PDT, 5 min illumination

Laser illumination, 10 minutes DEVICE

Laser illumination will be delivered via the optical fiber for a duration of 10 minutes. The fluence rate will be set such that the maximum fluence rate at the abscess wall is 20 mW/cm2.

Also known as: Modulight ML7710-PDT Laser System

MB-PDT, 10 min illumination

Laser illumination, 15 minutes DEVICE

Laser illumination will be delivered via the optical fiber for a duration of 15 minutes. The fluence rate will be set such that the maximum fluence rate at the abscess wall is 20 mW/cm2.

Also known as: Modulight ML7710-PDT Laser System

MB-PDT, 15 min illumination

Laser illumination, 20 minutes DEVICE

Laser illumination will be delivered via the optical fiber for a duration of 20 minutes. The fluence rate will be set such that the maximum fluence rate at the abscess wall is 20 mW/cm2.

Also known as: Modulight ML7710-PDT Laser System

MB-PDT, 20 min illumination

Laser illumination, 25 minutes DEVICE

Laser illumination will be delivered via the optical fiber for a duration of 25 minutes. The fluence rate will be set such that the maximum fluence rate at the abscess wall is 20 mW/cm2.

Also known as: Modulight ML7710-PDT Laser System

MB-PDT, 25 min illumination

Laser illumination, 30 minutes DEVICE

Laser illumination will be delivered via the optical fiber for a duration of 30 minutes. The fluence rate will be set such that the maximum fluence rate at the abscess wall is 20 mW/cm2.

Also known as: Modulight ML7710-PDT Laser System

MB-PDT, 30 min illumination

Optical spectroscopy measurement DEVICE

A fiber-optic probe that has undergone high-level disinfection will be advanced through the drainage catheter/needle in order to make gentle contact with the wall of the cavity. Low-intensity white light will be delivered by a tungsten halogen lamp by a single fiber within the probe, and detected by eight other fibers within the probe. Following this, low-power laser light will be delivered by a fiber-coupled laser diode at 640 nm in order to excite methylene blue fluorescence. Emitted fluorescence will similarly be collected by the eight detection fibers contained within the probe. Upon completion of these measurements, the fiber-optic probe will be withdrawn, gently wiped with sterile gauze, and returned to the procedure cart.

MB-PDT, 10 min illumination; MB-PDT, 15 min illumination; MB-PDT, 20 min illumination; MB-PDT, 25 min illumination; MB-PDT, 30 min illumination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 years or older
• If female, patient must have negative pregnancy test
• All patients with clinical symptoms (ex: fever, chills, pain, tachycardia, hypotension), laboratory (leukocytosis) and radiologic findings (thick walled, rim-enhancing collection with gas bubbles or air-fluid levels) compatible with an abscess that requires image-guided percutaneous drainage
• Abscess cavity diameters will be less than or equal to 8 cm. However, abscess can be complex or loculated
• Approval by the primary care team to pursue PDT and discuss enrollment with the patient

You may not qualify if:

• Pregnancy
• Lactation
• Allergy to contrast media, narcotics, sedatives, atropine or eggs
• Necrotic tissue that requires surgical debridement
• Severely compromised cardiopulmonary function or hemodynamic instability
• Thrombocytopenia (\<50,000/mm3)
• Uncorrectable coagulopathy
• Poor kidney function (serum creatinine \>3mg/dl)
• Lack of a safe pathway to the abscess or fluid collection
• Unable or unwilling to understand or to provide informed consent
• Unable or unwilling to undergo study procedures
• Patient unable to cooperate with, or to be positioned for the procedure
• Unable to comply with necessary follow up
• Abscesses greater than 8 cm in diameter, multiple separate abscesses in different locations, and abscesses not amenable to safe percutaneous image-guided drainage.
• Patient is currently taking serotonergic psychiatric medication

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (6)

• Haidaris CG, Foster TH, Waldman DL, Mathes EJ, McNamara J, Curran T. Effective photodynamic therapy against microbial populations in human deep tissue abscess aspirates. Lasers Surg Med. 2013 Oct;45(8):509-16. doi: 10.1002/lsm.22171. Epub 2013 Aug 29.

  PMID: 23996629 BACKGROUND

• Baran TM, Bass DA, Christensen L, Longbine E, Favella MD, Foster TH, Sharma AK. Safety and Feasibility of Photodynamic Therapy for Percutaneous Image-guided Abdominopelvic Abscess Drainage: Phase 1 Trial. Radiology. 2024 Mar;310(3):e232667. doi: 10.1148/radiol.232667.

  PMID: 38501946 DERIVED

• Hannan MN, Sharma AK, Baran TM. First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy by in vivo diffuse reflectance spectroscopy. J Biomed Opt. 2024 Feb;29(2):027002. doi: 10.1117/1.JBO.29.2.027002. Epub 2024 Feb 27.

  PMID: 38414658 DERIVED

• Li Z, Hannan MN, Sharma AK, Baran TM. Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination. Phys Med Biol. 2024 Feb 28;69(5):055031. doi: 10.1088/1361-6560/ad2635.

  PMID: 38316055 DERIVED

• Li Z, Hannan MN, Sharma AK, Baran TM. Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination. medRxiv [Preprint]. 2023 Nov 6:2023.10.23.23297420. doi: 10.1101/2023.10.23.23297420.

  PMID: 37961683 DERIVED

• Baran TM, Sharma AK. Photodynamic Therapy of an Abdominal Abscess at the Time of Percutaneous Drainage. Cardiovasc Intervent Radiol. 2023 Sep;46(9):1292-1294. doi: 10.1007/s00270-023-03504-z. Epub 2023 Jul 18. No abstract available.

  PMID: 37464107 DERIVED

MeSH Terms

Conditions

Abscess

Interventions

Methylene Blue

Condition Hierarchy (Ancestors)

Suppuration; Infections; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Timothy M Baran, PhD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Ashwani K Sharma, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Laurie Christensen, BS

  University of Rochester

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 3, 2014
• First Posted: September 15, 2014
• Study Start: September 1, 2014
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: March 6, 2024

Record last verified: 2024-03

Locations

US (1)