xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05995873</url>
    </required_header>
    <id_info>
      <org_study_id>R44DA050358</org_study_id>
      <nct_id>NCT05995873</nct_id>
    </id_info>
    <brief_title>A Project to Test the Efficacy and Safety of An Innovative Treatment for Opiate Use Disorders.</brief_title>
    <official_title>A Project to Test the Efficacy and Safety of An Innovative Treatment for Opiate Use Disorders.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>MindLight, LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Mclean Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>MindLight, LLC</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Investigators will test, for safety and efficacy, a novel treatment for opiate addiction that&#xD;
        applies a 4-minute treatment of intense near infra-red light to stimulate a side of the brain&#xD;
        that the investigators determine to be healthier, more mature, and less traumatized.&#xD;
        Investigators will compare among actively using participants an active and a sham treatment&#xD;
        given either once or twice weekly for 25-weeks at 2 sites. Investigators hope this will lead&#xD;
        to a significant weapon in the battle against the opioid epidemic as well as lead to&#xD;
        psychological and physiological insights into possible relations among trauma, cerebral&#xD;
        laterality, and addiction.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Approach. Investigators have had a and productive Pre-submission meeting with the FDA on&#xD;
        April 21, 2022, and are following their guidance in our approach. The goal of this Phase II&#xD;
        study is to test further the efficacy and safety of a new and innovative, patented&#xD;
        application of transcranial photobiomodulation for the treatment of opioid use disorder&#xD;
        (defined by DSM-5 criteria) with the possibility of achieving FDA clearance. The Opioid&#xD;
        Addiction Therapy System is a photobiomodulation device platform intended to be used alone or&#xD;
        as an aid to psychotherapy and medical-assisted treatments to treat opioid use disorder. It&#xD;
        is intended to be used by trained psychotherapists in clinical environments on patients with&#xD;
        opioid use disorder.&#xD;
  &#xD;
        Specific Aim1:&#xD;
  &#xD;
          1. Following FDA's preliminary guidance, Investigators aim first to assess whether active&#xD;
             Rx with UtPBM administered to the more positive hemisphere helps participants taper and&#xD;
             abstain from use of opioids as indicated by an increase in the percent of weekly visits&#xD;
             in which there was no self-reported use of opioids on TimeLine Follow Back and urine&#xD;
             screens for opioids were negative. This will be assessed from weeks 10 through 26, to&#xD;
             give participants sufficient time to taper off opioids. An additional primary outcome&#xD;
             will be the reduction in frequency of use (days per week) as assessed using timeline&#xD;
             feedback from baseline to week 26. Secondary outcome measures will include the&#xD;
             following: retention in treatment, opioid craving, withdrawal symptoms, clinical global&#xD;
             impression ratings of severity and improvement, quality of life metrics and Treatment&#xD;
             Success, as at least 80% opioid abstinence during weeks 10-26. An assessment will also&#xD;
             be made of adverse events during the treatment period.&#xD;
  &#xD;
             Milestones: a. Investigators predict based on our Phase I findings that active treatment&#xD;
             will increase weekly abstinence rates by 20% or more over sham treatment (e.g., 30% vs&#xD;
             10% weekly opioid-negative visits). Investigators expect each of the secondary outcomes&#xD;
             to be significantly better in the active group with a p value of less than 0.05.&#xD;
  &#xD;
          2. Investigators wish to see if actively treated participants age more slowly over the&#xD;
             26-week course of the study than those who receive the sham treatments. Investigators&#xD;
             will measure this by using epigenetic techniques. Investigators will use&#xD;
             state-of-the-art epigenetic measures of Intrinsic Epigenetic Age Acceleration to assess&#xD;
             subtype differences in DNA m. Investigators feel this is superior focusing on candidate&#xD;
             genes. Peripheral lymphocytes are the most appropriate cell type for assessing Intrinsic&#xD;
             Epigenetic Age Acceleration.&#xD;
  &#xD;
        Sequence of Visits. Interested individuals will call to receive information and will complete&#xD;
        a brief screen for age and key exclusion criteria. Those who appear eligible will be invited&#xD;
        to interview. Visit 1 will consist of full study informed consent, structured interviews to&#xD;
        assess inclusion and exclusion criteria, TimeLine Followback to assess current degree of&#xD;
        substance use, urine drug screen and computerized assessment of hemispheric emotional&#xD;
        valence. Those who meet entrance criteria and agree to participate will be randomized into&#xD;
        active or sham groups. Treatment sessions will start with visit 1 and will occur twice weekly&#xD;
        for 6 weeks, then weekly until week 25 with one untreated follow-up session on week 26.&#xD;
  &#xD;
        Within Session Protocol. Participants will give verbal reconsent to be in the study at each&#xD;
        study session. Immediately before each UtPBM active and sham treatment, the primary and the&#xD;
        secondary outcome measures will be recorded.&#xD;
  &#xD;
        The active treatment will consist of applying PBM in the form of a super-luminous LED with an&#xD;
        output of 250 mW/cm2 at a frequency of 810 nM with a width of 40 nM when applied the skin for&#xD;
        a fluence of 60J/cm2. The treatment will consist of the exposure to the light for 4 minutes&#xD;
        at one of 2 sites on the forehead that correspond to the 10-20 electroencephalogram sites,&#xD;
        F3, and F4. Whether Investigators will treat at F3 or F4 will be determined by the tests of&#xD;
        HEV. Investigators will treat the side that is determined to have a more positive HEV. Based&#xD;
        on a penetration of 3.7% of the light to the dura, Investigators will be applying 2.1 Joules/&#xD;
        cm2 to the treated area of the brain. Our level of light exposure is well below the ANSI&#xD;
        standard of 0.32 W/cm2. The fluence of our device is 40 times less than the device that was&#xD;
        used in the study of 1410 stroke patients without any observed side-effects and was found in&#xD;
        a study of the rat brain exposed to light to cause no observable behavioral or cellular&#xD;
        alterations. The device has been determined by the FDA to be of no significant risk as&#xD;
        described in the attached FDA letter of September 8, 2022.&#xD;
  &#xD;
        The sham treatment will be identical to the active treatment except that the LED will be&#xD;
        covered with aluminum foil to prevent near-infrared light from reaching the brain. The&#xD;
        treating clinician, who will not be blinded, will apply the either the active or the sham&#xD;
        treatment to the participant in a manner that does not allow either the recording clinician&#xD;
        or the patient to have any way to detect whether a given treatment is active or sham. When&#xD;
        asked in prior studies, neither the patients nor recorders were able to detect whether the&#xD;
        application was active or sham at the time of treatment.&#xD;
  &#xD;
        Although Investigators believe that the procedures in this study are not expected to cause&#xD;
        adverse effects, during all procedures the researcher in attendance will closely observe the&#xD;
        subject for any adverse effects. All NIH and WCG IRB patient safety and monitoring procedures&#xD;
        will be followed. For any adverse events Investigators will use the NIH Adverse Events Form.&#xD;
        All serious adverse events will be report to the IRB, NIH and FDA and posted to&#xD;
        clinicaltrials.gov.&#xD;
  &#xD;
        Subjects will not wear protective eyewear. The researcher administering the tPBM will be&#xD;
        careful to not shine the LED into the subjects' eyes. LEDs do not pose the level of danger to&#xD;
        the eyes that lasers present because the LED light is not coherent; still a person's staring&#xD;
        into a super-luminous LED for 4-minutes could potentially cause damage the eye, but a second&#xD;
        or two of looking at the LED will not cause harm. Photobiomodulation is currently used to&#xD;
        treat some retinal diseases.&#xD;
  &#xD;
        Any subject who for any reason wishes to leave the study at any time before its conclusion,&#xD;
        of course, will be free to do so. If any unexpected, unacceptable adverse events are&#xD;
        observed, Investigators will discontinue the entire study until Investigators have fully&#xD;
        consulted with the IRB.&#xD;
  &#xD;
        Each session will include use assessment of frequency and extent of opioid and other&#xD;
        substances, urine analysis with temperature check for drug use, pregnancy testing of female&#xD;
        participants, assessment of hemispheric emotional valence, symptom ratings and active or sham&#xD;
        UtPBM. Following treatment, participants who revealed drug use, or had a positive urine&#xD;
        assay, will be provided with instructions on how to safely taper opioid use (e.g., 10-20%&#xD;
        reduction per week if using daily, discontinuation if using less frequently). Participants&#xD;
        who have reduced intake from baseline will also be cautioned at each visit that there is an&#xD;
        increased risk for overdose if they abruptly return to a previously used higher dose as it&#xD;
        can take as little as a week to lose tolerance.&#xD;
  &#xD;
        Investigators have extensive experience with our device and method and in clinical practice&#xD;
        and in a study, Investigators intentionally activated the negative hemisphere, and this can&#xD;
        cause the patient to feel his usual anxiety and symptoms but has never created a danger. All&#xD;
        treating personnel are well trained in our techniques. Investigators will not blame a failure&#xD;
        to reach our milestones on treatment of the wrong side; Investigators are testing our method&#xD;
        of determining the side of the greater HEV and treating it.&#xD;
  &#xD;
        Outcome Measures: Primary Measure of efficacy will be percent abstinence from opioid use,&#xD;
        defined as the percent of each participant's weekly visits that are negative for opioid use&#xD;
        both on the use report and by urine analysis from weeks 10-26. If a participant misses a&#xD;
        visit, Investigators will attempt to contact them by phone for a use rating and to have them&#xD;
        provide a urine sample at a test center. Otherwise, all missed samples or ratings will be&#xD;
        defined as non-negative. In addition, Investigators will also assess whether there was a&#xD;
        significant difference between active and sham treatment in the frequency (days per week) of&#xD;
        use based on the use report, which Investigators have found in our studies to reveal a&#xD;
        greater degree of use than once or twice weekly urine tests, and which provides more&#xD;
        granularity than designating each week (or test) as positive or negative. This is the&#xD;
        approach that Investigators used to analyze opioid use from the phase I study and makes sense&#xD;
        as the proposed protocol does not include a detoxification stage.&#xD;
  &#xD;
        Secondary Measures include the following standard outcome measures: retention in treatment,&#xD;
        opioid craving, withdrawal symptoms, clinical global impression ratings of severity and&#xD;
        improvement, and Treatment Success, as at least 80% opioid abstinence during weeks 10-26.&#xD;
        Secondary outcomes have been used in one or more of the RCTs designed to test the efficacy of&#xD;
        buprenorphine for opioid use disorder. Investigators will also include visual analog scale&#xD;
        ratings of quality of life and quality of relationships and the Hamilton Depression Rating&#xD;
        Scale and the Hamilton Anxiety Rating Scale.&#xD;
  &#xD;
        Opioid craving will be assessed using the Opioid Craving Visual Analog Scale (0-100 mm).&#xD;
        Withdrawal symptoms will be assessed using the Clinical Opioid Withdrawal Scale.&#xD;
        Investigators will also use the Subjective Opiate Withdraw Scale and the Columbia Suicide&#xD;
        Severity Scale. Retention will be assessed as the number of sessions attended as determined&#xD;
        by their discontinuation or removal. Participants will be removed from the study if they&#xD;
        engage in a dangerous or sexually inappropriate manner with staff or have a positive&#xD;
        pregnancy test. Investigators will conduct analyses of both discontinuation, which will&#xD;
        include all participants who fail to complete the full trial, and a specific analysis of the&#xD;
        voluntary drop-out rate that would include participants who exit the study, are lost to&#xD;
        follow up, receive medication assisted treatment or other somatic modalities, but would&#xD;
        exclude legitimate unavoidable reasons for discontinuation such as pregnancy, parole&#xD;
        violation or verifiable illness or injury unrelated to current opioid use disorder that would&#xD;
        preclude participation.&#xD;
  &#xD;
        Investigators will measure Intrinsic epigenetic age acceleration using the whole methylome&#xD;
        chip. For these analyses, Investigators will use the EWAS of that provides an epigenetic&#xD;
        measure of low-grade chronic inflammation from an additive weighted score of 58 replicated&#xD;
        CpG sites in European and African-Ancestry samples. Intrinsic epigenetic age acceleration&#xD;
        will be assessed from the Epic Methylome array. This parameter typically correlates highly&#xD;
        with chronological age, however, emerging evidence from our lab and others point to an&#xD;
        acceleration of epigenetic aging in response to cumulative lifetime stress, childhood&#xD;
        maltreatment, and post-traumatic stress disorder. All saliva samples will be stored and&#xD;
        processed at McLean Hospital which has specimen and data security in place.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 10, 2023</start_date>
    <completion_date type="Anticipated">July 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>130 participants will be treated with unilateral transcranial photobiomodulation to their brain hemisphere with a more positive emotional valence. Half will receive sham and half active. Treatment will be 2 times a week for 4 weeks, then once a week for 20 weeks and then a followup 1 week later. The study will be half at MindLight, LLC and half at McLean Hospital.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>Only the treater knows whether the participant receives the sham or active treatment.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>percent of participants that achieve abstenense</measure>
      <time_frame>up to 26 weeks</time_frame>
      <description>we will test for use with urine and hair test</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall clinical status</measure>
      <time_frame>at the end of the study</time_frame>
      <description>Clinical Global Impressions Scale</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">130</enrollment>
    <condition>Opioid Use Disorder, Moderate</condition>
    <condition>Opioid Use</condition>
    <condition>Opioid Dependence</condition>
    <condition>Opioid Abuse</condition>
    <condition>Opiate Dependence</condition>
    <condition>Opioid Use, Unspecified</condition>
    <arm_group>
      <arm_group_label>treatment</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>Half of the participants will receive sham. Treatment will be 2 times a week for 4 weeks, then once a week for 20 weeks and then a followup 1 week later. The sham device is identical to the active device except that it has foil over the LED.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Active treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in this group will receive a 4-minute unilateral transcranial photobiomodulation treatment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>unilateral transcranial photobiomodulation</intervention_name>
      <description>An 810nM LED at 240mW/cm2 is placed at either F3 or F4 for 4 minutes.</description>
      <arm_group_label>Active treatment</arm_group_label>
      <arm_group_label>treatment</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or non-pregnant females between 18-65 years of age&#xD;
  &#xD;
            -  Individuals having an opioid use disorder with mild-to-moderately severe symptoms&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Individuals who are pregnant,&#xD;
  &#xD;
            -  Individuals who are psychotic,&#xD;
  &#xD;
            -  Individuals who are actively suicidal,&#xD;
  &#xD;
            -  Individuals who are a danger to self or others,&#xD;
  &#xD;
            -  Individuals who are who have a history of severe psychiatric or neurological disorders&#xD;
               or life-threatening medical illness.&#xD;
  &#xD;
            -  Individuals will be excluded with chronic pain requiring opioid treatment.&#xD;
  &#xD;
            -  Individuals who are who are breastfeeding,&#xD;
  &#xD;
            -  Individuals who are adults requiring a legally authorized representative.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <link>
      <url>https://www.frontiersin.org/articles/10.3389/fpsyt.2021.713686/full</url>
      <description>Article: An Effective and Safe Novel Treatment of Opioid Use Disorder</description>
    </link>
    <reference>
      <citation>Schiffer F, Khan A, Bolger E, Flynn E, Seltzer WP, Teicher MH. An Effective and Safe Novel Treatment of Opioid Use Disorder: Unilateral Transcranial Photobiomodulation. Front Psychiatry. 2021 Aug 10;12:713686. doi: 10.3389/fpsyt.2021.713686. eCollection 2021.</citation>
      <PMID>34447323</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Opioid-Related Disorders</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05995873
  org study id: R44DA050358
  nct id: NCT05995873
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Investigators will test, for safety and efficacy, a novel treatment for opiate addiction that
        applies a 4-minute treatment of intense near infra-red light to stimulate a side of the brain
        that the investigators determine to be healthier, more mature, and less traumatized.
        Investigators will compare among actively using participants an active and a sham treatment
        given either once or twice weekly for 25-weeks at 2 sites. Investigators hope this will lead
        to a significant weapon in the battle against the opioid epidemic as well as lead to
        psychological and physiological insights into possible relations among trauma, cerebral
        laterality, and addiction.
  Approach. Investigators have had a and productive Pre-submission meeting with the FDA on
        April 21, 2022, and are following their guidance in our approach. The goal of this Phase II
        study is to test further the efficacy and safety of a new and innovative, patented
        application of transcranial photobiomodulation for the treatment of opioid use disorder
        (defined by DSM-5 criteria) with the possibility of achieving FDA clearance. The Opioid
        Addiction Therapy System is a photobiomodulation device platform intended to be used alone or
        as an aid to psychotherapy and medical-assisted treatments to treat opioid use disorder. It
        is intended to be used by trained psychotherapists in clinical environments on patients with
        opioid use disorder.
  
        Specific Aim1:
  
          1. Following FDA's preliminary guidance, Investigators aim first to assess whether active
             Rx with UtPBM administered to the more positive hemisphere helps participants taper and
             abstain from use of opioids as indicated by an increase in the percent of weekly visits
             in which there was no self-reported use of opioids on TimeLine Follow Back and urine
             screens for opioids were negative. This will be assessed from weeks 10 through 26, to
             give participants sufficient time to taper off opioids. An additional primary outcome
             will be the reduction in frequency of use (days per week) as assessed using timeline
             feedback from baseline to week 26. Secondary outcome measures will include the
             following: retention in treatment, opioid craving, withdrawal symptoms, clinical global
             impression ratings of severity and improvement, quality of life metrics and Treatment
             Success, as at least 80% opioid abstinence during weeks 10-26. An assessment will also
             be made of adverse events during the treatment period.
  
             Milestones: a. Investigators predict based on our Phase I findings that active treatment
             will increase weekly abstinence rates by 20% or more over sham treatment (e.g., 30% vs
             10% weekly opioid-negative visits). Investigators expect each of the secondary outcomes
             to be significantly better in the active group with a p value of less than 0.05.
  
          2. Investigators wish to see if actively treated participants age more slowly over the
             26-week course of the study than those who receive the sham treatments. Investigators
             will measure this by using epigenetic techniques. Investigators will use
             state-of-the-art epigenetic measures of Intrinsic Epigenetic Age Acceleration to assess
             subtype differences in DNA m. Investigators feel this is superior focusing on candidate
             genes. Peripheral lymphocytes are the most appropriate cell type for assessing Intrinsic
             Epigenetic Age Acceleration.
  
        Sequence of Visits. Interested individuals will call to receive information and will complete
        a brief screen for age and key exclusion criteria. Those who appear eligible will be invited
        to interview. Visit 1 will consist of full study informed consent, structured interviews to
        assess inclusion and exclusion criteria, TimeLine Followback to assess current degree of
        substance use, urine drug screen and computerized assessment of hemispheric emotional
        valence. Those who meet entrance criteria and agree to participate will be randomized into
        active or sham groups. Treatment sessions will start with visit 1 and will occur twice weekly
        for 6 weeks, then weekly until week 25 with one untreated follow-up session on week 26.
  
        Within Session Protocol. Participants will give verbal reconsent to be in the study at each
        study session. Immediately before each UtPBM active and sham treatment, the primary and the
        secondary outcome measures will be recorded.
  
        The active treatment will consist of applying PBM in the form of a super-luminous LED with an
        output of 250 mW/cm2 at a frequency of 810 nM with a width of 40 nM when applied the skin for
        a fluence of 60J/cm2. The treatment will consist of the exposure to the light for 4 minutes
        at one of 2 sites on the forehead that correspond to the 10-20 electroencephalogram sites,
        F3, and F4. Whether Investigators will treat at F3 or F4 will be determined by the tests of
        HEV. Investigators will treat the side that is determined to have a more positive HEV. Based
        on a penetration of 3.7% of the light to the dura, Investigators will be applying 2.1 Joules/
        cm2 to the treated area of the brain. Our level of light exposure is well below the ANSI
        standard of 0.32 W/cm2. The fluence of our device is 40 times less than the device that was
        used in the study of 1410 stroke patients without any observed side-effects and was found in
        a study of the rat brain exposed to light to cause no observable behavioral or cellular
        alterations. The device has been determined by the FDA to be of no significant risk as
        described in the attached FDA letter of September 8, 2022.
  
        The sham treatment will be identical to the active treatment except that the LED will be
        covered with aluminum foil to prevent near-infrared light from reaching the brain. The
        treating clinician, who will not be blinded, will apply the either the active or the sham
        treatment to the participant in a manner that does not allow either the recording clinician
        or the patient to have any way to detect whether a given treatment is active or sham. When
        asked in prior studies, neither the patients nor recorders were able to detect whether the
        application was active or sham at the time of treatment.
  
        Although Investigators believe that the procedures in this study are not expected to cause
        adverse effects, during all procedures the researcher in attendance will closely observe the
        subject for any adverse effects. All NIH and WCG IRB patient safety and monitoring procedures
        will be followed. For any adverse events Investigators will use the NIH Adverse Events Form.
        All serious adverse events will be report to the IRB, NIH and FDA and posted to
        clinicaltrials.gov.
  
        Subjects will not wear protective eyewear. The researcher administering the tPBM will be
        careful to not shine the LED into the subjects' eyes. LEDs do not pose the level of danger to
        the eyes that lasers present because the LED light is not coherent; still a person's staring
        into a super-luminous LED for 4-minutes could potentially cause damage the eye, but a second
        or two of looking at the LED will not cause harm. Photobiomodulation is currently used to
        treat some retinal diseases.
  
        Any subject who for any reason wishes to leave the study at any time before its conclusion,
        of course, will be free to do so. If any unexpected, unacceptable adverse events are
        observed, Investigators will discontinue the entire study until Investigators have fully
        consulted with the IRB.
  
        Each session will include use assessment of frequency and extent of opioid and other
        substances, urine analysis with temperature check for drug use, pregnancy testing of female
        participants, assessment of hemispheric emotional valence, symptom ratings and active or sham
        UtPBM. Following treatment, participants who revealed drug use, or had a positive urine
        assay, will be provided with instructions on how to safely taper opioid use (e.g., 10-20%
        reduction per week if using daily, discontinuation if using less frequently). Participants
        who have reduced intake from baseline will also be cautioned at each visit that there is an
        increased risk for overdose if they abruptly return to a previously used higher dose as it
        can take as little as a week to lose tolerance.
  
        Investigators have extensive experience with our device and method and in clinical practice
        and in a study, Investigators intentionally activated the negative hemisphere, and this can
        cause the patient to feel his usual anxiety and symptoms but has never created a danger. All
        treating personnel are well trained in our techniques. Investigators will not blame a failure
        to reach our milestones on treatment of the wrong side; Investigators are testing our method
        of determining the side of the greater HEV and treating it.
  
        Outcome Measures: Primary Measure of efficacy will be percent abstinence from opioid use,
        defined as the percent of each participant's weekly visits that are negative for opioid use
        both on the use report and by urine analysis from weeks 10-26. If a participant misses a
        visit, Investigators will attempt to contact them by phone for a use rating and to have them
        provide a urine sample at a test center. Otherwise, all missed samples or ratings will be
        defined as non-negative. In addition, Investigators will also assess whether there was a
        significant difference between active and sham treatment in the frequency (days per week) of
        use based on the use report, which Investigators have found in our studies to reveal a
        greater degree of use than once or twice weekly urine tests, and which provides more
        granularity than designating each week (or test) as positive or negative. This is the
        approach that Investigators used to analyze opioid use from the phase I study and makes sense
        as the proposed protocol does not include a detoxification stage.
  
        Secondary Measures include the following standard outcome measures: retention in treatment,
        opioid craving, withdrawal symptoms, clinical global impression ratings of severity and
        improvement, and Treatment Success, as at least 80% opioid abstinence during weeks 10-26.
        Secondary outcomes have been used in one or more of the RCTs designed to test the efficacy of
        buprenorphine for opioid use disorder. Investigators will also include visual analog scale
        ratings of quality of life and quality of relationships and the Hamilton Depression Rating
        Scale and the Hamilton Anxiety Rating Scale.
  
        Opioid craving will be assessed using the Opioid Craving Visual Analog Scale (0-100 mm).
        Withdrawal symptoms will be assessed using the Clinical Opioid Withdrawal Scale.
        Investigators will also use the Subjective Opiate Withdraw Scale and the Columbia Suicide
        Severity Scale. Retention will be assessed as the number of sessions attended as determined
        by their discontinuation or removal. Participants will be removed from the study if they
        engage in a dangerous or sexually inappropriate manner with staff or have a positive
        pregnancy test. Investigators will conduct analyses of both discontinuation, which will
        include all participants who fail to complete the full trial, and a specific analysis of the
        voluntary drop-out rate that would include participants who exit the study, are lost to
        follow up, receive medication assisted treatment or other somatic modalities, but would
        exclude legitimate unavoidable reasons for discontinuation such as pregnancy, parole
        violation or verifiable illness or injury unrelated to current opioid use disorder that would
        preclude participation.
  
        Investigators will measure Intrinsic epigenetic age acceleration using the whole methylome
        chip. For these analyses, Investigators will use the EWAS of that provides an epigenetic
        measure of low-grade chronic inflammation from an additive weighted score of 58 replicated
        CpG sites in European and African-Ancestry samples. Intrinsic epigenetic age acceleration
        will be assessed from the Epic Methylome array. This parameter typically correlates highly
        with chronological age, however, emerging evidence from our lab and others point to an
        acceleration of epigenetic aging in response to cumulative lifetime stress, childhood
        maltreatment, and post-traumatic stress disorder. All saliva samples will be stored and
        processed at McLean Hospital which has specimen and data security in place.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: 130 participants will be treated with unilateral transcranial photobiomodulation to their brain hemisphere with a more positive emotional valence. Half will receive sham and half active. Treatment will be 2 times a week for 4 weeks, then once a week for 20 weeks and then a followup 1 week later. The study will be half at MindLight, LLC and half at McLean Hospital.
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: Only the treater knows whether the participant receives the sham or active treatment.
  measure: percent of participants that achieve abstenense
  time frame: up to 26 weeks
  description: we will test for use with urine and hair test
  measure: Overall clinical status
  time frame: at the end of the study
  description: Clinical Global Impressions Scale
  arm group label: treatment
  arm group type: Sham Comparator
  description: Half of the participants will receive sham. Treatment will be 2 times a week for 4 weeks, then once a week for 20 weeks and then a followup 1 week later. The sham device is identical to the active device except that it has foil over the LED.
  arm group label: Active treatment
  arm group type: Experimental
  description: Participants in this group will receive a 4-minute unilateral transcranial photobiomodulation treatment.
  intervention type: Device
  intervention name: unilateral transcranial photobiomodulation
  description: An 810nM LED at 240mW/cm2 is placed at either F3 or F4 for 4 minutes.
  arm group label: Active treatment
  arm group label: treatment
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  url: https://www.frontiersin.org/articles/10.3389/fpsyt.2021.713686/full
  description: Article: An Effective and Safe Novel Treatment of Opioid Use Disorder
  citation: Schiffer F, Khan A, Bolger E, Flynn E, Seltzer WP, Teicher MH. An Effective and Safe Novel Treatment of Opioid Use Disorder: Unilateral Transcranial Photobiomodulation. Front Psychiatry. 2021 Aug 10;12:713686. doi: 10.3389/fpsyt.2021.713686. eCollection 2021.
  PMID: 34447323
  responsible party type: Sponsor
  mesh term: Opioid-Related Disorders