Posttraumatic Stress DisorderPhase 4ATLASNCT07862712
Assessing Trauma-related Links Between Affective and Metabolic Systems
A Phase 4 study testing prazosin in people with Posttraumatic Stress Disorder and Metabolic Syndrome, run by VA Office of Research and Development at 1 site in United States.
Trial summary
KEY INFORMATION: The purpose of this study is to understand how insulin resistance (how your body processes sugar) and PTSD might be related. The goal is to improve the health of Veterans in three ways: 1. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Posttraumatic Stress Disorder, Metabolic Syndrome, Insulin Resistance
- What is being tested?
- prazosin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2027to 31 Dec 2032
- Phase
- Phase 4
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veteran of the US military
- Diagnosis of post-traumatic stress disorder (PTSD) defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) symptom count on Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Who cannot join
- Any form of diabetes as defined by the American Diabetes Association. Exceptions may be made for participants with previously undiagnosed, early, asymptomatic Type 2 Diabetes Mellitus (T2DM) who meet American Diabetes Association criteria for diabetes during study screening who wish to be included
- Diagnosis of DSM-5-defined bipolar I, schizophrenia spectrum or other psychotic disorders (by MINI)
- Diagnosis of dementia or related progressive neurocognitive disorder, based on clinical records
- Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 months
- Current use or use within the past 2 weeks of a medication with significant 1-AR or 2-AR activity (prazosin, doxazosin, alfuzosin, clonidine, guanfacine), or opiates
- Current use or use within the past 3 months of antipsychotics, glucocorticoid medications, or glucose-lowering medications, including but not limited to metformin and GLP-1 agonists
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- Contraindication to prazosin
- History of moderate or severe Traumatic Brain Injury (TBI) as defined by the Ohio State University TBI Identification Method
- Increased risk of suicide that necessitates inpatient treatment, intensive outpatient care, or treatment excluded by the protocol
- Pregnancy or lactation, or anticipated pregnancy at any point during study participation
- Ongoing or initiation of new treatment with evidence-based trauma-focused therapy for post-traumatic stress disorder (PTSD) within 2 weeks of baseline. Supportive psychotherapy may be continued during the study.
- Current enrollment in another interventional trial for post-traumatic stress disorder (PTSD)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108-1532
Katharine J Liang, MD PhD, (206) 277-6538, katharine.liang@va.gov
Carolyn L Fort, BS, (206) 768-5259, carolyn.fort@va.gov
About this study
Official title: From Hyperarousal to Hyperglycemia: Therapeutic Targeting of Noradrenergic Signaling in PTSD-Related Insulin Resistance
KEY INFORMATION: The purpose of this study is to understand how insulin resistance (how your body processes sugar) and PTSD might be related. The goal is to improve the health of Veterans in three ways:
- Understanding health risks: The investigators want to learn why Veterans with post-traumatic stress disorder (PTSD) are more likely to develop medical problems related to insulin resistance, such as diabetes.
- Testing effects of a medication: The investigators are testing whether prazosin, a medication that studies have shown may address some PTSD symptoms, can also improve how the body responds to insulin. If it does, this could point to a specific biological pathway that could be targeted for development of new treatments to prevent insulin resistance and diabetes in Veterans with PTSD.
- Links to depression. The investigators will also look at whether insulin sensitivity affects depression symptoms in people with PTSD. This may inform future research into treatments for PTSD.
Read the detailed description
Background and Study Objective: Post-traumatic stress disorder (PTSD) affects as many as 15% of Veterans following deployment and is associated with high rates of medical comorbidities linked to insulin resistance (IR), which is present in over half of people with PTSD. PTSD severity is prospectively associated with increased risk of both worsening IR severity and new-onset type 2 diabetes mellitus, leading to premature mortality. Biological effects of trauma exposure are linked to downstream disruption of both brain and metabolic processes, with mounting evidence that trauma-related mechanisms leading to IR may be biologically distinct from that of IR in the general population. One potential mechanism linking trauma exposure to IR lies in studies of noradrenaline (NA) blockade, with 1 adrenoreceptor antagonists demonstrating benefit for insulin sensitivity in patients with IR and hypertension. While a substantial body of evidence supports a role for increased NA signaling in PTSD, the potential link between NA and IR in the context of PTSD deserves further investigation. This connection suggests that increased IR following trauma also has the potential to play a causal role in the generation of psychiatric symptoms, particularly depressive symptoms, with multiple studies suggesting a potential causal relationship of IR on depressive symptoms. Defining mechanistic links between mental health and metabolic disorders have important clinical implications that may improve our approach to treating both mental and physical health disorders in Veterans with a history of trauma.
Study Design and Methods: Interrelationships among NA signaling (estimated by standing systolic blood pressure), insulin sensitivity (estimated by Oral Glucose Insulin Sensitivity index), and mental health symptoms will be examined in a population of Veterans with current PTSD. The effect of prazosin-mediated 1 adrenoreceptor antagonism on insulin sensitivity will be assessed in an open label single-arm interventional clinical trial design, with exploratory analysis of a potential mediating effect of improved insulin sensitivity on improvement in depression. These measures will be used to test the hypotheses pertaining to Veterans with PTSD: (1) increased NA signaling and hyperarousal symptoms are associated with lowered insulin sensitivity, (2) lowered insulin sensitivity is associated with elevated depression symptoms, (3) insulin sensitivity will improve with prazosin-mediated 1 antagonism, and (4) improvement in insulin sensitivity will be associated with improvement in depressive symptoms in response to prazosin.
This work is expected to contribute to Veteran's health in three major ways: (1) The investigators are investigating biological mechanisms in Veterans with insulin resistance and PTSD. If this is successful, it will contribute to our understanding of why Veterans with PTSD are at increased risk for comorbid medical conditions related to insulin resistance such as diabetes. (2) The investigators are testing whether noradrenergic blockade with the medication prazosin, currently used to treat PTSD, affects insulin sensitivity in Veterans with PTSD. If successful, this would identify a specific biological pathway that could be targeted for development of novel pharmacotherapeutic approaches to insulin resistance and downstream diabetes in Veterans with PTSD. (3) Our results may also provide information about the effect of insulin sensitivity on depressive symptoms in PTSD. This information has potential to contribute to the development of new strategies for treating, or even preventing, depression in PTSD, as well as overall PTSD treatment strategies.
- Being tested
- prazosin
- Keywords
- Stress Disorders, Post-Traumatic, Metabolic Syndrome, Insulin Resistance
- Medical subject headings
- Stress Disorders, Post-Traumatic, Metabolic Syndrome, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prazosinDrug
Also called Minipress
All participants will receive prazosin for 12 weeks according to a titration schedule informed by our prior studies, up to a minimum of 1mg in the morning and 3mg at night, up to a total daily dose of 16mg as tolerated. Higher doses may be considered as clinically appropriate.
| Study group | Role | What they receive |
|---|---|---|
| Prazosin | Experimental | The investigators will collect mental health and metabolic measures before and after prazosin treatment Receives: Drug: prazosin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Noradrenergic signaling and insulin sensitivity
Correlation between baseline noradrenergic signaling (standing systolic blood pressure) and insulin sensitivity (OGIS)
Measured: 5 years
Insulin sensitivity change after prazosin
Change in insulin sensitivity (OGIS) in response to prazosin
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2026
- Study start1 Mar 2027 (estimated)
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Katharine J Liang, MD PhD, Principal investigator, VA Puget Sound Health Care System Seattle Division, Seattle, WA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07862712
- Sponsor's protocol ID
- MHBP-012-25F
- Other IDs
- K2-RD002695-01-A2
- Acronym
- ATLAS
- Status last verified
- Oct 2026
- First submitted
- 1 Oct 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- From Hyperarousal to Hyperglycemia: Therapeutic Targeting of Noradrenergic Signaling in PTSD-Related Insulin Resistance
- ClinicalTrials.gov ID
- NCT07862712
- Acronym / sponsor ID
- ATLAS / MHBP-012-25F
- Keywords
- Stress Disorders, Post-Traumatic, Metabolic Syndrome, Insulin Resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Mar 2027 (estimated)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 7 Oct 2026 (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.
KEY INFORMATION: The purpose of this study is to understand how insulin resistance (how your body processes sugar) and PTSD might be related. The goal is to improve the health of Veterans in three ways:
- Understanding health risks: The investigators want to learn why Veterans with post-traumatic stress disorder (PTSD) are more likely to develop medical problems related to insulin resistance, such as diabetes.
- Testing effects of a medication: The investigators are testing whether prazosin, a medication that studies have shown may address some PTSD symptoms, can also improve how the body responds to insulin. If it does, this could point to a specific biological pathway that could be targeted for development of new treatments to prevent insulin resistance and diabetes in Veterans with PTSD.
- Links to depression. The investigators will also look at whether insulin sensitivity affects depression symptoms in people with PTSD. This may inform future research into treatments for PTSD.
Detailed description
Background and Study Objective: Post-traumatic stress disorder (PTSD) affects as many as 15% of Veterans following deployment and is associated with high rates of medical comorbidities linked to insulin resistance (IR), which is present in over half of people with PTSD. PTSD severity is prospectively associated with increased risk of both worsening IR severity and new-onset type 2 diabetes mellitus, leading to premature mortality. Biological effects of trauma exposure are linked to downstream disruption of both brain and metabolic processes, with mounting evidence that trauma-related mechanisms leading to IR may be biologically distinct from that of IR in the general population. One potential mechanism linking trauma exposure to IR lies in studies of noradrenaline (NA) blockade, with 1 adrenoreceptor antagonists demonstrating benefit for insulin sensitivity in patients with IR and hypertension. While a substantial body of evidence supports a role for increased NA signaling in PTSD, the potential link between NA and IR in the context of PTSD deserves further investigation. This connection suggests that increased IR following trauma also has the potential to play a causal role in the generation of psychiatric symptoms, particularly depressive symptoms, with multiple studies suggesting a potential causal relationship of IR on depressive symptoms. Defining mechanistic links between mental health and metabolic disorders have important clinical implications that may improve our approach to treating both mental and physical health disorders in Veterans with a history of trauma.
Study Design and Methods: Interrelationships among NA signaling (estimated by standing systolic blood pressure), insulin sensitivity (estimated by Oral Glucose Insulin Sensitivity index), and mental health symptoms will be examined in a population of Veterans with current PTSD. The effect of prazosin-mediated 1 adrenoreceptor antagonism on insulin sensitivity will be assessed in an open label single-arm interventional clinical trial design, with exploratory analysis of a potential mediating effect of improved insulin sensitivity on improvement in depression. These measures will be used to test the hypotheses pertaining to Veterans with PTSD: (1) increased NA signaling and hyperarousal symptoms are associated with lowered insulin sensitivity, (2) lowered insulin sensitivity is associated with elevated depression symptoms, (3) insulin sensitivity will improve with prazosin-mediated 1 antagonism, and (4) improvement in insulin sensitivity will be associated with improvement in depressive symptoms in response to prazosin.
This work is expected to contribute to Veteran's health in three major ways: (1) The investigators are investigating biological mechanisms in Veterans with insulin resistance and PTSD. If this is successful, it will contribute to our understanding of why Veterans with PTSD are at increased risk for comorbid medical conditions related to insulin resistance such as diabetes. (2) The investigators are testing whether noradrenergic blockade with the medication prazosin, currently used to treat PTSD, affects insulin sensitivity in Veterans with PTSD. If successful, this would identify a specific biological pathway that could be targeted for development of novel pharmacotherapeutic approaches to insulin resistance and downstream diabetes in Veterans with PTSD. (3) Our results may also provide information about the effect of insulin sensitivity on depressive symptoms in PTSD. This information has potential to contribute to the development of new strategies for treating, or even preventing, depression in PTSD, as well as overall PTSD treatment strategies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prazosin | Experimental | Drug: prazosinThe investigators will collect mental health and metabolic measures before and after prazosin treatment |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Veteran of the US military
- Diagnosis of post-traumatic stress disorder (PTSD) defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) symptom count on Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Key exclusion criteria (12 listed)
- Any form of diabetes as defined by the American Diabetes Association. Exceptions may be made for participants with previously undiagnosed, early, asymptomatic Type 2 Diabetes Mellitus (T2DM) who meet American Diabetes Association criteria for diabetes during study screening who wish to be included
- Diagnosis of DSM-5-defined bipolar I, schizophrenia spectrum or other psychotic disorders (by MINI)
- Diagnosis of dementia or related progressive neurocognitive disorder, based on clinical records
- Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 months
- Current use or use within the past 2 weeks of a medication with significant 1-AR or 2-AR activity (prazosin, doxazosin, alfuzosin, clonidine, guanfacine), or opiates
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 |
|---|---|---|
| prazosinAlso: MinipressAll participants will receive prazosin for 12 weeks according to a titration schedule informed by our prior studies, up to a minimum of 1mg in the morning and 3mg at night, up to a total daily dose of 16mg as tolerated. Higher doses may be considered as clinically appropriate. | Drug | Prazosin |
Primary outcome
Noradrenergic signaling and insulin sensitivity
Time frame: 5 years
Correlation between baseline noradrenergic signaling (standing systolic blood pressure) and insulin sensitivity (OGIS)
Insulin sensitivity change after prazosin
Time frame: 5 years
Change in insulin sensitivity (OGIS) in response to prazosin
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 15 Oct 2026.
- 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.
Katharine J Liang, MD PhD principal investigator
VA Puget Sound Health Care System Seattle Division, Seattle, WA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing prazosin in people with Posttraumatic Stress Disorder and Metabolic Syndrome, run by VA Office of Research and Development at 1 site 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 2 inclusion and 12 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: opening soon, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Katharine J Liang, MD PhD ((206) 277-6538, katharine.liang@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Noradrenergic signaling and insulin sensitivity (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.