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)
• Enrollment: 10
• Location: 1
• Arms: 2
• Actual Duration (Months): 24.2
• Patients Per Site Per Month: 0.4

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 Disease	Intervention/Treatment	Phase
Post-traumatic Stress Disorder (PTSD)	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Engineering Research Building (ERB), University of Texas Arlington	Arlington	Texas	United States	76010

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)

• Study Protocol - May 15, 2021
• Statistical Analysis Plan - May 15, 2021

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: Transcranial infrared laser stimulation (TILS); Near-infrared spectroscopy (NIRS)
• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic

Study Results

Participant Flow

Recruitment Details	31 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 Detail	All of the nine participants were randomly assigned into the two arms.

Arm/Group Title	One TILS, One Sham, and Then Five TILS Interventions	One Sham, Then Six TILS Interventions
Arm/Group Description	Participants 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
STARTED	6	3
COMPLETED	6	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	One TILS, One Sham, and Then Five TILS Interventions	One Sham, Then Six TILS Interventions	Total
Arm/Group Description	Participants 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 Participants	6	3	9
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

Title	Cerebral CCO Changes in Response to TILS and Sham
Description	Cerebral CCO changes measured by broadband NIRS during six TILS interventions and one sham session.
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One TILS, One Sham, and Then Five TILS Interventions	One Sham, Then Six TILS Interventions
Arm/Group Description	Participants 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 Participants	6	3
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

Title	Cerebral Hemodynamic Changes in Response to TILS and Sham
Description	Cerebral hemodynamic changes measured by broadband NIRS during every TILS or sham session
Time Frame	7 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One TILS, One Sham, and Then Five TILS Interventions	One Sham, Then Six TILS Interventions
Arm/Group Description	Participants 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 Participants	6	3
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

Title	Short-term Memory Scores
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One TILS, One Sham, and Then Five TILS Interventions	One Sham, Then Six TILS Interventions
Arm/Group Description	Participants 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 Participants	6	3
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

Title	Prefrontal Activations in Short-term Memory Processing
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	One TILS, One Sham, and Then Five TILS Interventions	One Sham, Then Six TILS Interventions
Arm/Group Description	Participants 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 Participants	6	3
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 Frame	Entire 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 Title	One TILS, One Sham, and Then Five TILS Interventions		One Sham, Then Six TILS Interventions
Arm/Group Description	Participants 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 Interventions		One Sham, Then Six TILS Interventions
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/3 (0%)
Serious Adverse Events
	One TILS, One Sham, and Then Five TILS Interventions		One Sham, Then Six TILS Interventions
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	One TILS, One Sham, and Then Five TILS Interventions		One Sham, Then Six TILS Interventions
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (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.