Perceptual Olfactory Bias
Conditions
Brief summary
The study will use a prospective design consisting of three phases. The phases are: 1. the development of the perceptual retraining treatment (PRT), 2. the evaluation of the treatment's feasibility and acceptability, and 3. an assessment of its efficacy. During the third phase, a pilot study will be conducted in which participants will be randomly assigned to either PRT or a waitlist control group in order to assess efficacy. Diagnostic information and eligibility criteria will be assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM) 4th ed. (SCID) and the Clinician Administered PTSD Scale for DSM-5 (CAPS-5).
Detailed description
This study will use clinical interviews, self-report measures, and behavioral assessments to evaluate the efficacy of the PRT protocol. The study will recruit approximately 30 veterans. The primary inclusionary criterion will be that participants must show some evidence of olfactory perceptual bias toward military-relevant stimuli (e.g., burning rubber, decay, fuel). Investigators are not requiring current suicidal ideation as an entry criterion because investigators believe that a fair percentage of veterans will have some suicidal ideation/intent but making this an entry requirement will limit the investigators ability to recruit given the tight timeline for the study. The study will consist of the development and evaluation of a novel intervention. The essential feature of this intervention is the use of a gradient of triggering smells (e.g., burning rubber, decay, fuel, etc.), to which participants will be systematically exposed in an effort to facilitate habituation to these odors. The PRT protocol will be administered over two 1-hour sessions. Participants will return 1 month after their final PRT protocol session to complete a battery of follow-up measures, as well as the CAPS-5. The primary outcome measures of interest are: olfactory perceptual bias (as measured by the olfactory bias assessment), suicidal ideation and behaviors (as measured by the Beck Suicide Scale and Depressive Symptom Inventory- Suicidality Subscale), and symptoms related to suicide, such as anxiety and trauma (as measured by the Beck Anxiety Inventory and PTSD Checklist for DSM-5, respectively).
Interventions
BEHAVIORALPerceptual Retraining Treatment
Perceptual retraining involves the systematic presentation of diluted malodors (i.e., odors perceived as threatening). For each individual, vials on either side of a pre-determined and ideographic detection threshold will be presented. During the retraining, participants will be given feedback to shift their bias away from the malodorous target stimuli. For example, in the context of diluted solutions participants will be given the feedback that they are correct when a neutral response is given to solutions that are above the starting threshold (stronger malodor) and incorrect when a target is endorsed that is below the starting threshold (weaker malodor).
BEHAVIORALSham Neutral training
Control condition using systematic presentation of diluted neutral-neutral odor pairs.
Sponsors
United States Department of Defense
Southeast Louisiana Veterans Health Care System
Florida State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* evidence of olfactory perceptual bias toward military-relevant stimuli (e.g., burning rubber, decay, fuel). * military combat exposure in Operation Iraqi Freedom, Enduring Freedom, or New Dawn. * Age 18-60.
Exclusion criteria
* Significant medical illness that compromises olfactory perception or tolerance (e.g., significant olfactory disease or dysfunction, cardiovascular disease, respiratory disorders, renal disease, epilepsy, stroke, and uncontrolled hypertension or migraines). * Evidence of imminent suicidal intent * Evidence of current or past psychotic-spectrum disorders, or uncontrolled bipolar disorder. * English speakers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Olfactory Perceptual Bias | Baseline, Week 1 | A participant's ability to detect an array of threatening malodor in neutral dilution gradients will be tested at baseline and after the second and final intervention session (one week after baseline). Perceptual bias is calculated as the percentage of correct responses (i.e., yes or no to detecting the malodor) on an odor over 6 trials for each of the 8 odors, at 25% and 33% dilution (i.e., over 96 trials). Larger positive percentages indicate greater habituation to the malodor, and therefore a training effect toward reducing threat bias (i.e., a positive effect on intervention outcomes). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 1 Month | Baseline, month 1 | The Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 (CAPS-5) was administered at the baseline appointment and 1-month follow-up appointment to assess PTSD symptom severity. All 20 of the CAPS-5 items are scored 0-4 and summed to calculate a total score, which ranges from 0-80. Higher scores indicate greater PTSD symptom severity. A difference score was calculated by subtracting the CAPS-5 score at 1-month from baseline, and averaged across each condition; thus, higher (positive) change scores are indicative of increases in PTSD symptom severity, whereas lower (negative) change scores are indicative of decreases in PTSD symptom severity. |
| Change in Suicidal Ideation Assessed Using the Depressive Symptom Inventory - Suicidality Subscale | Baseline, month 1 | The Depressive Symptom Inventory - Suicidality Subscale (DSI-SS) was administered at the baseline appointment and 1 month follow-up appointment to assess the severity of thoughts related suicidal ideation. All four items of the DSI-SS are scored on a 0-3 scale, with total possible sum scores ranging from 0-12; higher scores indicate greater severity of suicidal ideation. For the outcome measure reported, a difference score was calculated by subtracting DSI-SS scores at 1 month from DSI-SS scores at baseline, and averaged across conditions. DSI-SS change scores of zero reflect no change from baseline to 1 month. |
| Change in Beck Suicide Scale Scores From Baseline to 1 Month | Baseline, month 1 | The Beck Suicide Scale (BSS) was administered at the baseline appointment and 1-month follow-up appointment to assess thoughts and behaviors related to suicidal ideation, desire, and attempts. The BSS comprises 21 items rated on a 0-3 scale. The first 19 items are sum scored with total possible scores ranging from 0 - 38, with higher scores indicating greater severity of suicide risk. A difference scores was calculated by subtracting the BSS score at 1 month from BSS scores at baseline. Mean change scores of 0 reflect no change in BSS scores from baseline to 1 month. |
| Change in the Beck Anxiety Inventory-II From Baseline to 1 Month | Baseline, month 1 | The Beck Anxiety Inventory-II (BAI) was administered at the baseline appointment and 1-month follow-up appointment to assess symptom severity associated with anxious arousal. The BAI comprises 21 items rated on a 0-3 scale, which can be sum scored to calculate total scores ranging from 0 - 63. Higher scores on the BAI are indicative of greater anxious arousal. A difference scores was calculated by subtracting the BAI score at 1 month from BAI scores at baseline; thus, higher (positive) change scores are indicative of increases in anxious arousal, whereas lower (negative) change scores are indicative of decreases in anxious arousal. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the community. Assessments occurred at the Florida State University Anxiety and Behavioral Health Clinic. In total, 16 individuals were assessed for eligibility. Of these, 15 participants were randomized to an intervention condition, and 1 was excluded because they were not combat exposed.
Pre-assignment details
Of the 15 participants randomized to condition, 2 did not receive their allocated intervention (both in the Sensory Retraining Treatment \[i.e., active\] condition), because they withdrew from the study before the baseline appointment.
Participants by arm
| Arm | Count |
|---|---|
| Sensory Retraining Treatment (SRT) The retraining portion (SRT) will also involve the systematic presentation of diluted malodors. For each individual, vials on either side of their initial ideographic detection threshold established in the bias assessment phase will be presented. During the retraining, participants will be given feedback to shift their bias away from the malodorous target stimuli. For example, in the context of diluted solutions participants will be given the feedback that they are correct when a neutral response is given to solutions that are above the starting threshold (stronger malodor) and incorrect when a target is endorsed that is below the starting threshold (weaker malodor). | 6 |
| Sham Neutral Training (SNT) Approximately half of the participants will be randomized to the SNT condition designed to control for the effects of time and learning. In the SNT condition, participants will complete the same assessments (including the olfactory bias assessment), as well as a sham training consisting of neutral/neutral odor pairing dilutions, rather than the combat/neutral odor pairings as in the SRT. Following the one-month assessment, they will be given the option to complete the SRT. | 7 |
| Total | 13 |
Baseline characteristics
| Characteristic | Sensory Retraining Treatment (SRT) | Total | Sham Neutral Training (SNT) |
|---|---|---|---|
| Age, Continuous | 37.33 years STANDARD_DEVIATION 13.63 | 34.85 years STANDARD_DEVIATION 10.12 | 32.71 years STANDARD_DEVIATION 6.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment United States | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 13 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 0 / 6 | 0 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
Percent Change in Olfactory Perceptual Bias
A participant's ability to detect an array of threatening malodor in neutral dilution gradients will be tested at baseline and after the second and final intervention session (one week after baseline). Perceptual bias is calculated as the percentage of correct responses (i.e., yes or no to detecting the malodor) on an odor over 6 trials for each of the 8 odors, at 25% and 33% dilution (i.e., over 96 trials). Larger positive percentages indicate greater habituation to the malodor, and therefore a training effect toward reducing threat bias (i.e., a positive effect on intervention outcomes).
Time frame: Baseline, Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Perceptual Retraining Treatment (PRT) | Percent Change in Olfactory Perceptual Bias | 21.33 Percent of correctly identified odors | Standard Deviation 25.67 |
| Sham Neutral Training (SNT) | Percent Change in Olfactory Perceptual Bias | -5 Percent of correctly identified odors | Standard Deviation 23.7 |
p-value: 0.08ANOVA
Secondary
Change From Baseline in Mean Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 1 Month
The Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 (CAPS-5) was administered at the baseline appointment and 1-month follow-up appointment to assess PTSD symptom severity. All 20 of the CAPS-5 items are scored 0-4 and summed to calculate a total score, which ranges from 0-80. Higher scores indicate greater PTSD symptom severity. A difference score was calculated by subtracting the CAPS-5 score at 1-month from baseline, and averaged across each condition; thus, higher (positive) change scores are indicative of increases in PTSD symptom severity, whereas lower (negative) change scores are indicative of decreases in PTSD symptom severity.
Time frame: Baseline, month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Perceptual Retraining Treatment (PRT) | Change From Baseline in Mean Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 1 Month | -16.00 Score on the CAPS-5 | Standard Deviation 19.8 |
| Sham Neutral Training (SNT) | Change From Baseline in Mean Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 1 Month | 2.00 Score on the CAPS-5 | Standard Deviation 16.71 |
Comparison: Post-hoc estimates of observed power for the difference between group means was calculated to be .15.p-value: 0.39t-test, 2 sided
Secondary
Change in Beck Suicide Scale Scores From Baseline to 1 Month
The Beck Suicide Scale (BSS) was administered at the baseline appointment and 1-month follow-up appointment to assess thoughts and behaviors related to suicidal ideation, desire, and attempts. The BSS comprises 21 items rated on a 0-3 scale. The first 19 items are sum scored with total possible scores ranging from 0 - 38, with higher scores indicating greater severity of suicide risk. A difference scores was calculated by subtracting the BSS score at 1 month from BSS scores at baseline. Mean change scores of 0 reflect no change in BSS scores from baseline to 1 month.
Time frame: Baseline, month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Perceptual Retraining Treatment (PRT) | Change in Beck Suicide Scale Scores From Baseline to 1 Month | 0 Scores on the BSS | Standard Deviation 0 |
| Sham Neutral Training (SNT) | Change in Beck Suicide Scale Scores From Baseline to 1 Month | 0 Scores on the BSS | Standard Deviation 0 |
Secondary
Change in Suicidal Ideation Assessed Using the Depressive Symptom Inventory - Suicidality Subscale
The Depressive Symptom Inventory - Suicidality Subscale (DSI-SS) was administered at the baseline appointment and 1 month follow-up appointment to assess the severity of thoughts related suicidal ideation. All four items of the DSI-SS are scored on a 0-3 scale, with total possible sum scores ranging from 0-12; higher scores indicate greater severity of suicidal ideation. For the outcome measure reported, a difference score was calculated by subtracting DSI-SS scores at 1 month from DSI-SS scores at baseline, and averaged across conditions. DSI-SS change scores of zero reflect no change from baseline to 1 month.
Time frame: Baseline, month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Perceptual Retraining Treatment (PRT) | Change in Suicidal Ideation Assessed Using the Depressive Symptom Inventory - Suicidality Subscale | 0 Scores on the DSI-SS | Standard Deviation 0 |
| Sham Neutral Training (SNT) | Change in Suicidal Ideation Assessed Using the Depressive Symptom Inventory - Suicidality Subscale | 0 Scores on the DSI-SS | Standard Deviation 0 |
Secondary
Change in the Beck Anxiety Inventory-II From Baseline to 1 Month
The Beck Anxiety Inventory-II (BAI) was administered at the baseline appointment and 1-month follow-up appointment to assess symptom severity associated with anxious arousal. The BAI comprises 21 items rated on a 0-3 scale, which can be sum scored to calculate total scores ranging from 0 - 63. Higher scores on the BAI are indicative of greater anxious arousal. A difference scores was calculated by subtracting the BAI score at 1 month from BAI scores at baseline; thus, higher (positive) change scores are indicative of increases in anxious arousal, whereas lower (negative) change scores are indicative of decreases in anxious arousal.
Time frame: Baseline, month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Perceptual Retraining Treatment (PRT) | Change in the Beck Anxiety Inventory-II From Baseline to 1 Month | -3.50 Scores on the BAI | Standard Deviation 0.71 |
| Sham Neutral Training (SNT) | Change in the Beck Anxiety Inventory-II From Baseline to 1 Month | -1.75 Scores on the BAI | Standard Deviation 3.5 |
Comparison: Post-hoc estimates of observed power for the difference between group means was calculated to be .08.p-value: 0.54t-test, 2 sided