Transcranial Infrared Laser Stimulation (TILS) of Prefrontal Cognition in Post-traumatic Stress Disorder (PTSD)

Sponsor
The University of Texas at Arlington (Other)
Overall Status
Terminated
CT.gov ID
NCT03209882
Collaborator
University of Texas at Austin (Other)
10
Enrollment
1
Location
2
Arms
24.2
Actual Duration (Months)
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the effects of transcranial infrared laser stimulation (TILS) on prefrontal metabolism and hemodynamics in veterans with post-traumatic stress disorder (PTSD). The subjects will receive six TILS interventions and one sham intervention in a course of seven weeks.

Condition or DiseaseIntervention/TreatmentPhase
  • Device: TILS
  • Device: sham
N/A

Detailed Description

Post-traumatic stress disorder (PTSD) is often associated with cognitive impairments. It has been indicated that hypoactivity of the prefrontal cortex plays a major role in the disrupted neural circuitry of mood and cognition.

Transcranial infrared laser stimulation (TILS) is a neural type of photobiomodulation that can elevate neuronal metabolism by exciting cytochrome c oxidase (CCO). Veterans with PTSD will receive prefrontal TILS interventions once-per-week for six weeks. They will also receive an additional sham intervention (laser power = 0) that will be randomly assigned into the first two sessions. Broadband near-infrared spectroscopy (bbNIRS) will be used to directly assess the CCO changes during every TILS/sham session.

Veterans' prefrontal functions will be evaluated with short-term memory tasks before and after each intervention. The prefrontal activities will also be imaged by functional near-infrared spectroscopy (fNIRS) to objectively assess the functional changes due to TILS/sham interventions.

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Single (Participant)
Primary Purpose:
Basic Science
Official Title:
Transcranial Infrared Laser Stimulation (TILS) of Prefrontal Metabolism and Function in Post-traumatic Stress Disorder (PTSD)
Actual Study Start Date :
Oct 1, 2017
Actual Primary Completion Date :
Oct 8, 2019
Actual Study Completion Date :
Oct 8, 2019

Arms and Interventions

ArmIntervention/Treatment
Experimental: One TILS, one sham, and then five TILS interventions

Participants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions.

Device: TILS
Continuous-wave laser of a specific wavelength (1064 nm) was administered to the participants' right forehead for 8 minutes. The laser power was 3.4 Watts.
Other Names:
  • Low-level laser therapy (LLLT)
  • Device: sham
    The sham session consisted of administering the same laser to the participants' right forehead for totally 8 minutes. However, the laser power was turned to be 0 Watts.

    Experimental: One sham, then six TILS interventions

    Participants first received a sham session, followed by six weekly TILS sessions.

    Device: TILS
    Continuous-wave laser of a specific wavelength (1064 nm) was administered to the participants' right forehead for 8 minutes. The laser power was 3.4 Watts.
    Other Names:
  • Low-level laser therapy (LLLT)
  • Device: sham
    The sham session consisted of administering the same laser to the participants' right forehead for totally 8 minutes. However, the laser power was turned to be 0 Watts.

    Outcome Measures

    Primary Outcome Measures

    1. Cerebral CCO Changes in Response to TILS and Sham [7 weeks]

      Cerebral CCO changes measured by broadband NIRS during six TILS interventions and one sham session.

    2. Cerebral Hemodynamic Changes in Response to TILS and Sham [7 weeks]

      Cerebral hemodynamic changes measured by broadband NIRS during every TILS or sham session

    Secondary Outcome Measures

    1. Short-term Memory Scores [8 weeks]

      The participant's recall time in Digit Forward (DF) task and Digit Backward (DB) task was recorded recorded during initial baseline, and after the one sham and six TILS sessions. The recall time indicates how fast the participants could recall that digital numbers 10 seconds after they vanished on computer screen.

    2. Prefrontal Activations in Short-term Memory Processing [8 weeks]

      Anterior prefrontal hemodynamic activations (HbO2 and Hb changes) measured by functional NIRS during the Digit Forward (DF) and Digit Backward (DB) tasks. The activations were recorded from initial baseline, and after the one sham and six TILS sessions. In post-experiment processing, the activations were averaged in the recall phase, which was a key component related to PTSD.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • War-zone and non-war-zone veterans

    • Ages 18-60 years old

    • Males and females

    • Able to read, speak, and understand English

    • Medical records showing prior diagnosis of PTSD (here it refers to the records prior to TILS, which will be assessed and obtained in Visit 1)

    • Medical records showing diagnosis of PTSD (here it refers to the CAPS-5 record prior to TILS, which will be assessed and obtained in Visit 1)

    • On stable doses of any psychotropic medications for at least 4 weeks

    Exclusion Criteria:
    • Significant physical disability to perform a computerized memory task

    • Past/current significant medical/neurological/mental health disorders known to affect cognitive functioning (e.g., stroke, dementia, schizophrenia, AIDS)

    • Presence of moderate/severe TBI, defined as having: alteration of consciousness/mental state >24 hours; posttraumatic amnesia >1 day; loss of consciousness >30 minutes; and/or abnormal structural neuroimaging. We will not exclude veterans with mild TBI, which is found in nearly 50% of veterans with PTSD

    • Alcohol abuse/dependence for the past 12- months, as determined by the Rapid Alcohol Problems Screen score >0

    • Drug abuse/dependence for the past 12- months, as determined by the Drug Abuse Screening Test-10 score >2

    • Severe depression (PHQ-9 total score >19), significant risk of suicide (SBQ-R >6), severe headache (PHQ-15, Item e =2), and/or severe dizziness (PHQ-15, Item g =2)

    • Opiate use in the month prior to study entry

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Engineering Research Building (ERB), University of Texas ArlingtonArlingtonTexasUnited States76010

    Sponsors and Collaborators

    • The University of Texas at Arlington
    • University of Texas at Austin

    Investigators

    • Principal Investigator: Fenghua Tian, PhD, University of Texas at Arlington

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Fenghua Tian, PhD, Assistant Professor of Research, The University of Texas at Arlington
    ClinicalTrials.gov Identifier:
    NCT03209882
    Other Study ID Numbers:
    • 2017-0512
    First Posted:
    Jul 6, 2017
    Last Update Posted:
    Jul 23, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Fenghua Tian, PhD, Assistant Professor of Research, The University of Texas at Arlington
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details31 veterans were screened for eligibility between October, 2017 and November, 2018. Ten veterans met the inclusion criteria, among them nine completed the study, and one quit after the initial screening for family reason.
    Pre-assignment DetailAll of the nine participants were randomly assigned into the two arms.
    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions.Participants first received a sham session, followed by six weekly TILS sessions.
    Period Title: Overall Study
    STARTED63
    COMPLETED63
    NOT COMPLETED00

    Baseline Characteristics

    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS InterventionsTotal
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions.Participants first received a sham session, followed by six weekly TILS sessions.Total of all reporting groups
    Overall Participants639
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    100%
    3
    100%
    9
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    36.3
    (12.7)
    36.33
    (12.7)
    36.3
    (12.7)
    Sex: Female, Male (Count of Participants)
    Female
    1
    16.7%
    1
    33.3%
    2
    22.2%
    Male
    5
    83.3%
    2
    66.7%
    7
    77.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    16.7%
    2
    66.7%
    3
    33.3%
    Not Hispanic or Latino
    5
    83.3%
    1
    33.3%
    6
    66.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    16.7%
    0
    0%
    1
    11.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    16.7%
    0
    0%
    1
    11.1%
    White
    3
    50%
    3
    100%
    6
    66.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    16.7%
    0
    0%
    1
    11.1%

    Outcome Measures

    1. Primary Outcome
    TitleCerebral CCO Changes in Response to TILS and Sham
    DescriptionCerebral CCO changes measured by broadband NIRS during six TILS interventions and one sham session.
    Time Frame7 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions.Participants first received a sham session, followed by six weekly TILS sessions.
    Measure Participants63
    Average CCO changes in response to sham
    0.09
    (0.21)
    -0.33
    (0.58)
    Average CCO changes in response to 1st TILS
    0.13
    (0.23)
    0.70
    (1.22)
    Average CCO changes in response to 2nd TILS
    0.03
    (0.27)
    1.44
    (2.58)
    Average CCO changes in response to 3rd TILS
    0.04
    (0.26)
    2.39
    (4.18)
    Average CCO changes in response to 4th TILS
    -0.12
    (0.57)
    0.86
    (1.75)
    Average CCO changes in response to 5th TILS
    0.08
    (0.23)
    0.47
    (1.01)
    Average CCO changes in response to 6th TILS
    0.09
    (0.13)
    1.03
    (1.78)
    2. Primary Outcome
    TitleCerebral Hemodynamic Changes in Response to TILS and Sham
    DescriptionCerebral hemodynamic changes measured by broadband NIRS during every TILS or sham session
    Time Frame7 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions.Participants first received a sham session, followed by six weekly TILS sessions.
    Measure Participants63
    Average deoxy-Hb change in response to sham
    0.40
    (0.26)
    -0.95
    (1.85)
    Average oxy-Hb change in response to sham
    0.28
    (1.76)
    -1.12
    (2.56)
    Average oxy-Hb change in response to 1st TILS
    2.80
    (1.71)
    2.77
    (5.13)
    Average deoxy-Hb change in response to 1st TILS
    0.08
    (0.47)
    1.66
    (2.03)
    Average oxy-Hb change in response to 2nd TILS
    3.08
    (1.57)
    3.58
    (3.97)
    Average deoxy-Hb change in response to 2nd TILS
    0.37
    (0.27)
    2.52
    (3.53)
    Average oxy-Hb change in response to 3rd TILS
    3.97
    (1.44)
    2.60
    (2.43)
    Average deoxy-Hb change in response to 3rd TILS
    0.12
    (0.21)
    3.37
    (5.42)
    Average oxy-Hb change in response to 4th TILS
    2.92
    (2.19)
    2.77
    (3.01)
    Average deoxy-Hb change in response to 4th TILS
    0.21
    (0.48)
    1.89
    (3.51)
    Average oxy-Hb change in response to 5th TILS
    2.44
    (1.23)
    3.05
    (1.45)
    Average deoxy-Hb change in response to 5th TILS
    0.64
    (0.54)
    1.04
    (2.26)
    Average oxy-Hb change in response to 6th TILS
    2.73
    (1.60)
    4.93
    (4.10)
    Average deoxy-Hb change in response to 6th TILS
    0.07
    (0.65)
    1.31
    (3.61)
    3. Secondary Outcome
    TitleShort-term Memory Scores
    DescriptionThe participant's recall time in Digit Forward (DF) task and Digit Backward (DB) task was recorded recorded during initial baseline, and after the one sham and six TILS sessions. The recall time indicates how fast the participants could recall that digital numbers 10 seconds after they vanished on computer screen.
    Time Frame8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions. TILS: Continuous-wave laser of a specific wavelength (1064 nm) was administered to the participants' right forehead for 8 minutes. The laser power was 3.4 Watts. sham: The sham session consisted of administering the same laser to the participants' right forehead for totally 8 minutes. However, the laser power was turned to be 0 Watts.Participants first received a sham session, followed by six weekly TILS sessions. TILS: Continuous-wave laser of a specific wavelength (1064 nm) was administered to the participants' right forehead for 8 minutes. The laser power was 3.4 Watts. sham: The sham session consisted of administering the same laser to the participants' right forehead for totally 8 minutes. However, the laser power was turned to be 0 Watts.
    Measure Participants63
    DF recall time, baseline
    7.1
    (2.9)
    6.5
    (3.4)
    DB recall time, baseline
    10.8
    (4.8)
    9.5
    (3.7)
    DF recall time, sham
    5.4
    (1.3)
    5.7
    (2.5)
    DB recall time, sham
    8.1
    (2.7)
    8.6
    (3.3)
    DF recall time, 1st TILS
    6.1
    (2.3)
    5.9
    (3.3)
    DB recall time, 1st TILS
    8.4
    (2.9)
    9.9
    (6.9)
    DF recall time, 2nd TILS
    5.6
    (1.4)
    5.9
    (2.8)
    DB recall time, 2nd TILS
    8.4
    (2.7)
    9.2
    (5.8)
    DF recall time, 3rd TILS
    5.2
    (1.1)
    5.9
    (3.5)
    DB recall time, 3rd TILS
    7.4
    (1.7)
    11.1
    (7.3)
    DF recall time, 4th TILS
    5.0
    (1.0)
    6.3
    (3.1)
    DB recall time, 4th TILS
    6.3
    (1.0)
    7.9
    (5.0)
    DF recall time, 5th TILS
    5.1
    (0.9)
    5.6
    (3.4)
    DB recall time, 5th TILS
    6.2
    (1.2)
    8.5
    (5.5)
    DF recall time, 6th TILS
    4.9
    (0.6)
    5.7
    (3.3)
    DB recall time, 6th TILS
    6.5
    (1.5)
    7.9
    (4.6)
    4. Secondary Outcome
    TitlePrefrontal Activations in Short-term Memory Processing
    DescriptionAnterior prefrontal hemodynamic activations (HbO2 and Hb changes) measured by functional NIRS during the Digit Forward (DF) and Digit Backward (DB) tasks. The activations were recorded from initial baseline, and after the one sham and six TILS sessions. In post-experiment processing, the activations were averaged in the recall phase, which was a key component related to PTSD.
    Time Frame8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions. TILS: Continuous-wave laser of a specific wavelength (1064 nm) was administered to the participants' right forehead for 8 minutes. The laser power was 3.4 Watts. sham: The sham session consisted of administering the same laser to the participants' right forehead for totally 8 minutes. However, the laser power was turned to be 0 Watts.Participants first received a sham session, followed by six weekly TILS sessions. TILS: Continuous-wave laser of a specific wavelength (1064 nm) was administered to the participants' right forehead for 8 minutes. The laser power was 3.4 Watts. sham: The sham session consisted of administering the same laser to the participants' right forehead for totally 8 minutes. However, the laser power was turned to be 0 Watts.
    Measure Participants63
    DF HbO2, baseline
    0.5
    (2.2)
    0.5
    (1.4)
    DF Hb, baseline
    -0.4
    (0.4)
    -0.8
    (1.5)
    DB HbO2, baseline
    1.4
    (2.2)
    -0.5
    (2.0)
    DB Hb, baseline
    0.7
    (1.0)
    0.3
    (0.5)
    DF HbO2, sham
    -0.6
    (3.1)
    -2.3
    (1.7)
    DF Hb, sham
    0.0
    (0.7)
    -0.3
    (0.4)
    DB HbO2, sham
    -1.1
    (2.7)
    -0.7
    (1.1)
    DB Hb, sham
    -0.1
    (1.2)
    0.2
    (0.4)
    DF HbO2, 1st TILS
    0.0
    (2.0)
    -1.2
    (1.3)
    DF Hb, 1st TILS
    0.0
    (0.5)
    0.1
    (0.5)
    DB HbO2, 1st TILS
    -2.5
    (4.0)
    -1.4
    (4.4)
    DB Hb, 1st TILS
    -0.5
    (1.3)
    0.4
    (1.1)
    DF HbO2, 2nd TILS
    -2.6
    (0.8)
    0.8
    (3.8)
    DF Hb, 2nd TILS
    -0.1
    (0.6)
    -1.1
    (2.6)
    DB HbO2, 2nd TILS
    1.0
    (2.0)
    3.9
    (9.6)
    DB Hb, 2nd TILS
    0.7
    (1.1)
    2.2
    (3.5)
    DF HbO2, 3rd TILS
    -1.0
    (1.7)
    0.6
    (4.0)
    DF Hb, 3rd TILS
    -0.2
    (0.3)
    0.8
    (0.2)
    DB HbO2, 3rd TILS
    -3.3
    (2.2)
    -1.0
    (1.0)
    DB Hb, 3rd TILS
    -1.1
    (1.1)
    0.1
    (0.4)
    DF HbO2, 4th TILS
    -1.6
    (2.8)
    -1.8
    (1.8)
    DF Hb, 4th TILS
    0.1
    (0.7)
    0.1
    (0.3)
    DB HbO2, 4th TILS
    -1.3
    (3.4)
    -1.1
    (3.7)
    DB Hb, 4th TILS
    -0.1
    (0.6)
    -0.8
    (1.0)
    DF HbO2, 5th TILS
    -3.2
    (2.0)
    0.6
    (2.0)
    DF Hb, 5th TILS
    -0.3
    (1.0)
    0.4
    (0.3)
    DB HbO2, 5th TILS
    -2.8
    (3.5)
    0.6
    (3.0)
    DB Hb, 5th TILS
    0.2
    (1.0)
    0.4
    (0.5)
    DF HbO2, 6th TILS
    -2.0
    (1.2)
    -0.4
    (1.5)
    DF Hb, 6th TILS
    -0.1
    (0.9)
    0.4
    (0.7)
    DB HbO2, 6th TILS
    0.4
    (2.9)
    -5.7
    (8.4)
    DB Hb, 6th TILS
    0.2
    (1.4)
    0.3
    (0.3)

    Adverse Events

    Time FrameEntire course of TILS/sham sessions (7 weeks).
    Adverse Event Reporting Description The subjects were closely monitored in regard to physical reactions to TILS, and worsening symptoms. A 10-level VAS scale was used to measure headache and dizziness following each TILS/sham session. Severe reaction was defined as VAS ≥5. Then, the subjects were assessed for worsening PTSD symptoms (an increase of ≥24 points in Mississippi-Military), severe depression (PHQ-9 > 19), risk of suicide(SBQ-R ≥ 7).
    Arm/Group TitleOne TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Arm/Group DescriptionParticipants first received a TILS intervention, followed by a sham session one week later. Then, participants received another five weekly TILS interventions.Participants first received a sham session, followed by six weekly TILS sessions.
    All Cause Mortality
    One TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/6 (0%) 0/3 (0%)
    Serious Adverse Events
    One TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/6 (0%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    One TILS, One Sham, and Then Five TILS InterventionsOne Sham, Then Six TILS Interventions
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/6 (0%) 0/3 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleFenghua Tian
    OrganizationUniversity of Texas at Arlington
    Phone8178075271
    Emailfenghua.tian@gmail.com
    Responsible Party:
    Fenghua Tian, PhD, Assistant Professor of Research, The University of Texas at Arlington
    ClinicalTrials.gov Identifier:
    NCT03209882
    Other Study ID Numbers:
    • 2017-0512
    First Posted:
    Jul 6, 2017
    Last Update Posted:
    Jul 23, 2021
    Last Verified:
    Jun 1, 2021