PTSDPhase 2NCT04558112
Improving Therapeutic Learning for PTSD
A Phase 2 study testing L-DOPA in people with PTSD and Post Traumatic Stress Disorder, run by University of Wisconsin, Madison at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- PTSD, Post Traumatic Stress Disorder
- What is being tested?
- L-DOPA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Feb 2021to Dec 2023
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Current diagnosis of PTSD where the index traumatic event includes physical or sexual assault
- English speaking
- Medically healthy
Who cannot join
- internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.)
- major medical disorders (such as cancer)
- psychotic disorders
- neurocognitive disorders
- developmental disorders
- pregnancy
Show all 29Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 1 recruiting
- Recruiting
University of Texas
Austin, Texas, 78701
Josh Cisler, PhD
- Completed
University of Wisconsin
Madison, Wisconsin, 53593
About this study
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.
Read the 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.
- Conditions
- PTSD, Post Traumatic Stress Disorder
- Being tested
- L-DOPA, Placebo
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-DOPADrug
two gel capsules with 100mg L-DOPA (with 25 mg carbidopa to inhibit peripheral decarboxylase)
PlaceboDrug
two gel capsules of placebo
| Study group | Role | What they receive |
|---|---|---|
| 100 mg L-DOPA | Experimental | 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. Receives: Drug: L-DOPA |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 2 days
Secondary outcomes (3)
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
Measured: up to 2 days
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
Measured: up to 2 days
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.
Measured: up to 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2020
- Study start18 Feb 2021
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Zachary Stowe, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04558112
- Sponsor's protocol ID
- 2019-1567
- Other IDs
- SMPH/PSYCHIATRY/PSYCHIATRY, 4R33MH108753-03, A538900, Protocol Version 6/26/2023
- Status last verified
- Jul 2023
- First submitted
- 15 Sep 2020
- Last updated
- 30 Aug 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cisler JM, Malloy LT, Jaeb M, Dunsmoor JE, Stowe ZN. Semantic encoding of trauma memories in the hippocampus among individuals with PTSD. Neuropsychopharmacology. 2026 Aug;51(9):1690-1698. doi: 10.1038/s41386-026-02402-5. Epub 2026 Apr 14.
PubMed 41981270
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Therapeutic Learning for PTSD
- ClinicalTrials.gov ID
- NCT04558112
- Acronym / sponsor ID
- 2019-1567
- Conditions
- PTSD, Post Traumatic Stress Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 18 Feb 2021 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 22 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 100 mg L-DOPA | Experimental | Drug: L-DOPAComplete 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. |
| Placebo | Placebo comparator | Drug: PlaceboComplete 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. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Current diagnosis of PTSD where the index traumatic event includes physical or sexual assault
- English speaking
- Medically healthy
Key exclusion criteria (29 listed)
- internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.)
- major medical disorders (such as cancer)
- psychotic disorders
- neurocognitive disorders
- developmental disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-DOPAtwo gel capsules with 100mg L-DOPA (with 25 mg carbidopa to inhibit peripheral decarboxylase) | Drug | 100 mg L-DOPA |
| Placebotwo gel capsules of placebo | Drug | Placebo |
Primary outcome
Change in negative emotional responding to trauma scripts on Day 2 compared to Day 1
Time frame: up to 2 days
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
3 secondary outcomes
Change in Skin Conductance Response (SCR) to trauma scripts on Day 2 compared to Day 1
Time frame: up to 2 days
Change in Heart Rate (HR) to trauma scripts on Day 2 compared to Day 1
Time frame: up to 2 days
Change in amygdala-hippocampus functional connectivity on Day 2 compared to Day 1
Time frame: up to 2 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2023.
- Derived from this study: PubMed 41981270Cisler JM, Malloy LT, Jaeb M, Dunsmoor JE, Stowe ZN. Semantic encoding of trauma memories in the hippocampus among individuals with PTSD. Neuropsychopharmacology. 2026 Aug;51(9):1690-1698. doi: 10.1038/s41386-026-02402-5. Epub 2026 Apr 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zachary Stowe, MD principal investigator
University of Wisconsin, Madison
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-DOPA in people with PTSD and Post Traumatic Stress Disorder, run by University of Wisconsin, Madison at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rachel Williams (608-262-6375, rmwilliams5@wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in negative emotional responding to trauma scripts on Day 2 compared to Day 1 (time frame: up to 2 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04558112, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2023.