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Improving Therapeutic Learning for PTSD

Primary Purpose

PTSD, Post Traumatic Stress Disorder

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
L-DOPA
Placebo
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PTSD

Eligibility Criteria

21 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Current diagnosis of PTSD where the index traumatic event includes physical or sexual assault
  • English speaking
  • Medically healthy

Exclusion Criteria:

  • internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.)
  • major medical disorders (such as cancer)
  • psychotic disorders
  • neurocognitive disorders
  • developmental disorders
  • active substance use disorders
  • pregnancy
  • breastfeeding
  • use of Monoamine oxidase inhibitors (MAO-I) in past two weeks is exclusionary

Additional Exclusion Criteria at UT-Austin:

  • heart disease
  • hepatic impairment
  • peptic ulcer disease
  • COPD
  • prescription medications that may interact with L-DOPA will not be permitted during a predetermined wash-out period

Due to safety concerns, participants with these conditions will be ineligible to participate:

  • Claustrophobia, or the inability to lie still in a confined space
  • Major medical disorders (e.g., HIV, cancer)
  • Magnetic metallic implants (such as screws, pins, shrapnel remnants, aneurysm clips, artificial heart valves, inner ear (cochlear) implants, artificial joints, and vascular stents), as these may heat, pull, or twist in the strong magnetic field of the MRI scanner
  • Electronic or magnetic implants, such as pacemakers, as these may stop working
  • Permanent makeup or tattoos with metallic dyes
  • A positive pregnancy test (for females), since the effect of strong magnetic fields and L-Dopa on the developing fetus remains unknown and inconclusive. (all female participants of childbearing potential will have a pregnancy test on the day of the MRI scan. Participants who test positive would be notified of this positive result)
  • A self-reported history of loss of consciousness (greater than 30 minutes)
  • Physical disabilities that prohibit task performance (such as blindness or deafness)
  • Psychotic disorders (e.g., schizophrenia)
  • Any other condition that the investigator believes might put the participant at risk

Due to their effects on image quality, participants with the following MAY be ineligible to participate per Principal Investigator's judgment:

  • Medications which may affect image quality (e.g., water pills)
  • Nonremovable dental implants, such as braces or upper permanent retainers, as these will distort the MRI images we collect (note: filings, crowns, and silver or gold teeth are OK)
  • Any other condition, medication, or implant that the investigator believes would degrade image quality or render data unusable

Sites / Locations

  • University of TexasRecruiting
  • University of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

100 mg L-DOPA

Placebo

Arm Description

Complete a ~40 min fMRI scan with either hearing their trauma or neutral narrative, ingest a pill (placebo or 100mg L-DOPA) upon leaving the scanner and wait in a waiting room for ~45 minutes, then undergo a 7 min resting-state fMRI scan.Participants return ~24 hours later for Day 2 fMRI, in which they will complete a single ~40-minute fMRI scan while listening to either their trauma or neutral narrative.

Complete a ~40 min fMRI scan with either hearing their trauma or neutral narrative, ingest a pill (placebo or 100mg L-DOPA) upon leaving the scanner and wait in a waiting room for ~45 minutes, then undergo a 7 min resting-state fMRI scan.Participants return ~24 hours later for Day 2 fMRI, in which they will complete a single ~40-minute fMRI scan while listening to either their trauma or neutral narrative.

Outcomes

Primary Outcome Measures

Change in negative emotional responding to trauma scripts on Day 2 compared to Day 1
Measured periodically through the narrative with a 10-point Likert scale of anxiety/distress (self-reported), with higher numbers indicating increased anxiety/distress. Measured on day 1 and day 2

Secondary Outcome Measures

Change in Skin Conductance Response (SCR) to trauma scripts on Day 2 compared to Day 1
SCR data will be acquired on a BIOPAC MP150 Data Acquisition System (BIOPAC Systems, Inc.) with electrodes placed on participant's left hand. Average intensity of participant skin conductance will be reported. Measured on day 1 and day 2
Change in Heart Rate (HR) to trauma scripts on Day 2 compared to Day 1
Heart rate data will be acquired with a pulse oximeter placed on participant's left hand. Average intensity of participant heart rate will be reported. Measured on day 1 and day 2
Change in amygdala-hippocampus functional connectivity on Day 2 compared to Day 1
Measured by 3T functioning magnetic resident imaging (fMRI), time courses of activity of the hippocampus and amygdala will be correlated on day 1 and day 2, then compared between the groups.

Full Information

First Posted
September 15, 2020
Last Updated
August 29, 2023
Sponsor
University of Wisconsin, Madison
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT04558112
Brief Title
Improving Therapeutic Learning for PTSD
Official Title
Improving Therapeutic Learning for PTSD
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 18, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The proposed project seeks to demonstrate the engagement of post-exposure dopamine neurotransmission and downstream acute reorganization of dopaminergic resting-state neural networks as a means of increasing consolidation of extinction memories formed during analogue exposure therapy in adult women with PTSD. Participants will include 120 women aged 21-50 with a current diagnosis of PTSD related to physical or sexual assault, English speaking, and medically healthy. Participants will complete the stages of the study across 2-3 days, depending on participant need.
Detailed Description
Specific Aim 1: Test the degree to which exogeneous manipulations of dopamine neurotransmission affect exposure therapy learning across multiple indices. Hypothesis: L-DOPA will decrease measures of fear responding across indices. Specific Aim 2: Test the degree to which post-exposure functional connectivity within dopaminergic neural networks mediates the effect of dopaminergic manipulation on fear responding after exposure therapy. Hypothesis: L-DOPA will predict enhanced post-exposure dopaminergic functional connectivity, which in turn predicts decrease fear recall.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PTSD, Post Traumatic Stress Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
100 mg L-DOPA
Arm Type
Experimental
Arm Description
Complete a ~40 min fMRI scan with either hearing their trauma or neutral narrative, ingest a pill (placebo or 100mg L-DOPA) upon leaving the scanner and wait in a waiting room for ~45 minutes, then undergo a 7 min resting-state fMRI scan.Participants return ~24 hours later for Day 2 fMRI, in which they will complete a single ~40-minute fMRI scan while listening to either their trauma or neutral narrative.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Complete a ~40 min fMRI scan with either hearing their trauma or neutral narrative, ingest a pill (placebo or 100mg L-DOPA) upon leaving the scanner and wait in a waiting room for ~45 minutes, then undergo a 7 min resting-state fMRI scan.Participants return ~24 hours later for Day 2 fMRI, in which they will complete a single ~40-minute fMRI scan while listening to either their trauma or neutral narrative.
Intervention Type
Drug
Intervention Name(s)
L-DOPA
Intervention Description
two gel capsules with 100mg L-DOPA (with 25 mg carbidopa to inhibit peripheral decarboxylase)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
two gel capsules of placebo
Primary Outcome Measure Information:
Title
Change in negative emotional responding to trauma scripts on Day 2 compared to Day 1
Description
Measured periodically through the narrative with a 10-point Likert scale of anxiety/distress (self-reported), with higher numbers indicating increased anxiety/distress. Measured on day 1 and day 2
Time Frame
up to 2 days
Secondary Outcome Measure Information:
Title
Change in Skin Conductance Response (SCR) to trauma scripts on Day 2 compared to Day 1
Description
SCR data will be acquired on a BIOPAC MP150 Data Acquisition System (BIOPAC Systems, Inc.) with electrodes placed on participant's left hand. Average intensity of participant skin conductance will be reported. Measured on day 1 and day 2
Time Frame
up to 2 days
Title
Change in Heart Rate (HR) to trauma scripts on Day 2 compared to Day 1
Description
Heart rate data will be acquired with a pulse oximeter placed on participant's left hand. Average intensity of participant heart rate will be reported. Measured on day 1 and day 2
Time Frame
up to 2 days
Title
Change in amygdala-hippocampus functional connectivity on Day 2 compared to Day 1
Description
Measured by 3T functioning magnetic resident imaging (fMRI), time courses of activity of the hippocampus and amygdala will be correlated on day 1 and day 2, then compared between the groups.
Time Frame
up to 2 days

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Current diagnosis of PTSD where the index traumatic event includes physical or sexual assault English speaking Medically healthy Exclusion Criteria: internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.) major medical disorders (such as cancer) psychotic disorders neurocognitive disorders developmental disorders pregnancy breastfeeding use of Monoamine oxidase inhibitors (MAO-I) in past two weeks is exclusionary Additional Exclusion Criteria at UT-Austin: heart disease hepatic impairment peptic ulcer disease COPD prescription medications that may interact with L-DOPA will not be permitted during a predetermined wash-out period Due to safety concerns, participants with these conditions will be ineligible to participate: Claustrophobia, or the inability to lie still in a confined space Major medical disorders (e.g., HIV, cancer) Magnetic metallic implants (such as screws, pins, shrapnel remnants, aneurysm clips, artificial heart valves, inner ear (cochlear) implants, artificial joints, and vascular stents), as these may heat, pull, or twist in the strong magnetic field of the MRI scanner Electronic or magnetic implants, such as pacemakers, as these may stop working Permanent makeup or tattoos with metallic dyes A positive pregnancy test (for females), since the effect of strong magnetic fields and L-Dopa on the developing fetus remains unknown and inconclusive. (all female participants of childbearing potential will have a pregnancy test on the day of the MRI scan. Participants who test positive would be notified of this positive result) A self-reported history of loss of consciousness (greater than 30 minutes) Physical disabilities that prohibit task performance (such as blindness or deafness) Psychotic disorders (e.g., schizophrenia) Any other condition that the investigator believes might put the participant at risk Due to their effects on image quality, participants with the following MAY be ineligible to participate per Principal Investigator's judgment: Medications which may affect image quality (e.g., water pills) Nonremovable dental implants, such as braces or upper permanent retainers, as these will distort the MRI images we collect (note: filings, crowns, and silver or gold teeth are OK) Any other condition, medication, or implant that the investigator believes would degrade image quality or render data unusable
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel Williams
Phone
608-262-6375
Email
rmwilliams5@wisc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zachary Stowe, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas
City
Austin
State/Province
Texas
ZIP/Postal Code
78701
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josh Cisler, PhD
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53593
Country
United States
Individual Site Status
Completed

12. IPD Sharing Statement

Plan to Share IPD
No

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Improving Therapeutic Learning for PTSD

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