Post Traumatic Stress DisorderPhase 2IV Allo PTSDNCT07079761
Facilitation of Extinction Retention and Reconsolidation Blockade by IV Allopregnanolone in PTSD.
A Phase 2 study testing Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer. and Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm in people with Post Traumatic Stress Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Purpose: About 6.4% of the U.S. population suffers from posttraumatic stress disorder (PTSD). Trauma-focused psychotherapies are generally effective in PTSD, but responses vary greatly across individuals and PTSD subpopulations. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Post Traumatic Stress Disorder
- What is being tested?
- Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer. and Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2025to 30 Apr 2027
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Between the ages of 18 and 55 (at time of enrollment), reproductively mature, and English speaking.
- Meet criteria for chronic PTSD (i.e., CAPS-5 determined PTSD duration more than 3 months).
- Generally healthy and not on any prohibited medications (that could affect study outcomes).
- Willing to abstain from alcohol for 2 weeks and from nicotine, marijuana or illicit drugs for 4 weeks before experimental procedures and throughout the study.
- For biological females:
- Natural menstrual cycle.
- If of childbearing potential, female and partner must use 2 types of effective birth control (except for hormonal contraceptives, unless IUD or a device like Nuvaring) for a week before the IV Allo or placebo infusion, and for one month after.
Who cannot join
- Present an imminent risk to self or others or require clinical intervention to maintain safety
- Diagnosis of moderate or severe substance use disorder within three months of screening per administration of the DIAMOND substance abuse evaluation. Diagnosis of a mild substance use disorder within three months of screening will be allowed if the participant agrees to abstain from illicit drugs for one month and/or alcohol for 2 weeks prior to the experimental procedures, has a negative screening or follow-up urine toxicology and/or saliva alcohol test (if the screening test is positive), and tests negative for these substances on the morning of the experimental procedures.
- Bipolar I disorder, schizophreniform disorders, or clinically significant psychotic symptoms apart from the presence of trauma-related sensory hallucinations or negative beliefs.
- History of a suicide attempt within 1 year of enrolling.
- A history of severe TBI is exclusionary for the PK-1 and PK-2 studies. A history of moderate or severe TBI is exclusionary for the main studies (i.e., Expt. 1 and Expt. 2).
- Diagnosis of sleep apnea
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- Awake resting O2 saturation < 96%
- Severe renal failure with an eGFR <30 ml/min
- Use of medications or substances (by report or toxicology testing) will be exclusionary under the following conditions:
- During screening for eligibility:
- Use of illicit substances, as well as prescribed opiates or benzodiazepines (either reported or detected on urine toxicology testing) will be exclusionary.
- Reported non-dependent use of cannabinoids or nicotine (indicated by a positive urine toxicology or cotinine test at screening) will not be exclusionary if the individual agrees to abstain from cannabinoids and nicotine for one month prior to the experimental procedures, has a follow-up negative screening test, and tests negative for these substances on the mornings of experimental procedures.
- A positive urine alcohol test at medical screening (which indicates uncontrolled alcohol use and likely moderate to severe alcohol dependence) will be exclusionary.
- A high serum gamma-glutamyl-transferase (GGT) test at screening (indicative of more remote recent drinking but not necessarily moderate to severe alcohol use or dependence) will not be exclusionary if the individual does not meet criteria for a moderate or severe alcohol use disorder within three months of screening, agrees to abstain from drinking for 2 weeks prior to the experimental procedures, and has normal follow-up urine alcohol and serum GGT tests.
- Use of non-illicit over the counter or prescribed medications that may increase the risk of IV Allo side effects or adversely affect the experimental results is exclusionary. Participants may agree to stop non-psychotropic medications used on a prn basis, such as acetaminophen, ibuprofen, or loratadine (a CYP3A inhibitor) for 5 half-lives of the parent drug or active metabolite (whichever is longer) before the experimental procedures. Regular psychotropic medications (including those used to treat non-psychiatric conditions, such as alpha1-antagonists prescribed for hypertension or urinary hesitancy) may be discontinued under the management of the potential participant's non-study prescriber for 3 months before evaluation for eligibility and participation in subsequent experimental procedures.
- On the mornings of the PK-1, PK-2, Expt. 1 or Expt. 2 experimental procedures:
- Use of any medications or substances that may increase the risk of IV Allo side effects or adversely affect the experimental results (indicated by report, urine toxicology, urine nicotine/cotinine testing, or urine alcohol testing) will be exclusionary.
- Systemic hormone therapy or contraception will be exclusionary [Exception: Hormonal IUDs (e.g., Mirena, Kyleena, Liletta, and Skyla) or other contraceptive devices (e.g., Nuvaring)] will be allowed if the participant still has normal menstrual periods and is found to ovulate using commercial urine test kits provided by study).
- Pregnancy (urine pregnancy tests given at each in-person session).
- Breast-feeding.
- Unable to tolerate IV placement or blood drawing by needle stick.
- Wear hearing aid(s) (For Expt. 1 and 2, not PK studies).
- Fail hearing test (For Expt. 1 and 2, not PK studies).
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, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Study Coordinator I, MS, 617-726-8508, kcurran0@mgh.harvard.edu
Study Coordinator II, BS, 617-726-8508, gbailey3@mgh.harvard.edu
About this study
Purpose: About 6.4% of the U.S. population suffers from posttraumatic stress disorder (PTSD). Trauma-focused psychotherapies are generally effective in PTSD, but responses vary greatly across individuals and PTSD subpopulations. Neurobiological factors impacted by life experiences, stress, and genetics can affect treatment responses. These factors can alter brain capacities needed to reprocess traumatic memories prevent them from triggering intensely distressing, disruptive, out-of-place responses.
For example, during psychotherapy for PTSD, trauma memory activation engages two competing brain processes that affect recovery: "extinction" versus "reconsolidation" of trauma-related emotional, physiological, and behavioral responses. This study tests whether a single intravenous (IV) dose of allopregnanolone (Allo) compared to placebo (which is non-active): promotes consolidation of extinction learning (sub-study 1) or blocks reconsolidation of physiological responses triggered by aversive memories (sub-study 2). The study also tests whether Allo compared to placebo affects retention of non-aversive memories.
Read the detailed description
Background: Allo is a neurosteroid (hormone) produced from progesterone by the brain, adrenal glands, testes, and ovaries. Production of Allo and its equally potent, structurally similar stereoisomer pregnanolone (PA) is stimulated when certain neurons in the brain are activated and when stress activates the adrenal glands. Allo and PA markedly increase effects of gamma-amino-butyric acid (GABA; an inhibitory neurotransmitter) in the brain, thereby regulating arousal and responses to stress. Allo and PA also influence processes that strengthen or weaken memories.
Basic research suggests that several factors can reduce production of Allo: exposure to chronic or extreme stress, prolonged social isolation, chronic intermittent heavy alcohol use, certain oral contraceptives, chronic use of some psychiatric medications or other substances used to manage PTSD such as nicotine, exposure to environment toxins, and genetic predisposition.
Research shows that Allo and PA production is reduced in a large subpopulation of women and men with PTSD. Reduced Allo and PA is strongly associated with PTSD severity and poor retention of extinction learning, both of which contribute to chronic PTSD. The proposed study thus will be conducted in adult men and women with chronic PTSD. Women will be studied during two distinct phases of the menstrual cycle because progesterone levels (and therefore levels of Allo and PA) change markedly across the menstrual cycle, as do problems with extinction retention.
Study Procedures: Eligible participants between 18 and 55 years of age will take part in a widely used, standardized 3-day laboratory psychophysiology paradigm during which activation of the sympathetic nervous system (fight/flight system) is monitored via small electrode patches placed on the skin. The paradigm involves startle testing on Days 1, 2 and 3. During startle testing, participants will hear sudden bursts of white noise through headphones, see colored shapes on a computer screen, and feel sudden (not painful) blasts of air to the neck. The electrodes record participants' eye blinks, skin conductance, and heart rate. The startling sounds will be about as loud as a train but last only a fraction of a second. Participants will sit quietly with their eyes open as they listen. On study Day 2, participants are randomized by "luck of the draw" or "chance" to receive either IV Allo or placebo. On study Days 2 and 3, a brief memory test also will be conducted. Blood is collected each day for measurement of Allo, PA and other neurobiological factors that may affect the potential beneficial effects of Allo. There will be a follow up phone session (about a week after the Day 3 visit/session).
Before starting the above studies, the investigators will conduct pharmacokinetic (PK) studies in a small group of individuals with PTSD to confirm that the selected IV Allo doses increase blood Allo levels as expected.
Implications: These studies may help us understand treatable factors that increase risk for chronic or treatment-resistant PTSD and PTSD-related depression. They may also tell us whether treatments that increase Allo might help prevent or treat PTSD. IV Allo (brexanolone) at much higher doses than used in this study) is currently FDA-approved for the treatment of postpartum depression, supporting the potential for this research to spur development of Allo as a new treatment for PTSD.
Study Population: About 96 individuals with PTSD (between 18-55 years of age) will be recruited to participate in these studies. Half of the women will be studied during the follicular phase of the menstrual cycle (after onset of menses) and half during the luteal phase (after ovulation). The study is being conducted at Massachusetts General Hospital, Boston, MA.
- Conditions
- Post Traumatic Stress Disorder
- Being tested
- Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer., Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Matching IV Placebo, Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm
- Keywords
- Trauma, Allopregnanolone, Neurosteroid
- Medical subject headings
- Stress Disorders, Post-Traumatic, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigmBehavioural
Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Extinction training will occur followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on extinction retention as well as reinstatement of conditioned psychophysiological reactions will be assessed.
Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.Drug
Also called U.S. P. equivalent: brexanolone (SAGE Therapeutics) (IV Allopregnanolone with Captisol)
On Day 2 of Experiment 1, a 1.7 mcg/kg dose of IV Allo will be administered over 5 minutes at the completion of extinction training to raise resting plasma Allo plus pregnanolone (PA) levels by 1500 pg/ml. This will be followed by a 4-5-hour continuous infusion of IV Allo at 2.6 mcg/kg/hr to maintain resting plasma Allo levels at the target level.
Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigmBehavioural
Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Extinction training will occur followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on extinction retention as well as reinstatement of conditioned psychophysiological reactions will be assessed.
Matching IV PlaceboOther
Also called 6% USP Dexolve alone in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.
On Day 2 of Experiment 1, participants randomized to placebo will receive IV matching placebo over 5 minutes at the completion of extinction training followed by a continuous infusion of matching placebo over the next 4-5 hours. The matching IV placebo will be administered according to the same per kg dosing regimen as that for active drug.
Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigmBehavioural
Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Brief exposure to the conditioned stimulus will be followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on reconsolidation blockade and reinstatement of conditioned psychophysiological reactions will be assessed.
Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.Drug
Also called U.S. P. equivalent: brexanolone (SAGE Therapeutics) (IV Allopregnanolone with Captisol)
On Day 2 of Experiment 2, a 28 mcg/kg dose of IV Allo will be infused over 30 minutes following brief reactivation of aversively conditioned psychophysiological reactions, after which IV fluid only (0.9% normal saline) will be administered over 4-5 hours.
Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigmBehavioural
Day 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Brief exposure to the conditioned stimulus will be followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on reconsolidation blockade and reinstatement of conditioned psychophysiological reactions will be assessed.
Matching IV PlaceboOther
Also called 6% USP Dexolve alone in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.
On Day 2 of Experiment 2, matching IV placebo will be infused over 30 minutes following brief reactivation of aversively conditioned psychophysiological reactions, after which IV fluid only (0.9% normal saline) will be administered over the 4-5 hours. The matching IV placebo will be administered according to the same per kg dosing regimen as that for active drug.
| Study group | Role | What they receive |
|---|---|---|
| IV Allopregnanolone (Allo) for Extinction Retention (Expt. 1) | Experimental | Arm 1 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after completion of extinction training. Receives: Behavioral: Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm; Drug: Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer. |
| IV Placebo for Extinction Retention (Expt. 1) | Placebo comparator | Arm 2 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after completion of extinction training. Receives: Behavioral: Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm; Other: Matching IV Placebo |
| IV Allo for Reconsolidation Blockade (Expt. 2) | Experimental | Arm 1 of Expt. 2 will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+). Receives: Behavioral: Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm; Drug: Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer. |
| IV Placebo for Reconsolidation Blockade (Expt. 2) | Placebo comparator | Arm 2 of Expt. 2 will include will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+). Receives: Behavioral: Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm; Other: Matching IV Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Experiment 1: Extinction retention
Extinction retention is calculated as a) the difference between the average skin conductance response (SCR) to the first 4 aversively conditioned stimulus (CS+) trials and the average SCR to first 4 neutral conditioned stimulus (CS-) trials on Day 3 minus b) the difference between the average SCR to the last 4 CS+ trials and last 4 CS- trials on Day 2.
Measured: Day 3
Experiment 2: Reconsolidation blockade
Reconsolidation blockade will be assessed by calculating the average fear potentiated startle (FPS) response to the first 4 CS+ trials on Day 3. Lower scores indicate better reconsolidation blockade.
Measured: Day 3
Secondary outcomes (4)
Experiment 1: Reinstatement of conditioned fear
Reinstatement of conditioned fear will be assessed by calculating the average SCR to the last 4 CS+ trials minus the average SCR to the last 4 CS- trials on Day 3.
Measured: Day 3
Experiment 2: Reinstatement of conditioned fear
Reinstatement of conditioned fear will be assessed as the average FPS to the last 4 CS+ trials on Day 3. Higher scores indicate greater reinstatement of conditioned fear.
Measured: Day 3
Reinstatement of Conditioned Fear in Expt. 1
Reinstatement of conditioned fear will be defined as the average SCR to the last 4 CS+ trials minus the average SCR to the last 4 CS- trials. For FPS, the last 4 CS+ trials will be examined. Higher scores indicate greater reinstatement of conditioned fear.
Measured: Day 3
Reinstatement of Conditioned Fear in Expt. 2
Reinstatement of conditioned fear will be defined as the average SCR to the last 4 CS+ trials minus the average SCR to the last 4 CS- trials. For FPS, the last 4 CS+ trials will be examined. Higher scores indicate greater reinstatement of conditioned fear.
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start4 Aug 2025
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Active drug vs. placebo will be administered in two separate experiments to a population of medically healthy, non-medicated patients with PTSD stratified by sex and by menstrual phase within female sex.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Ann M. Rasmusson, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07079761
- Sponsor's protocol ID
- 2025000693
- Other IDs
- 7R01MH122867-05
- Acronym
- IV Allo PTSD
- Status last verified
- Jul 2025
- First submitted
- 3 Jun 2025
- Last updated
- 5 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Facilitation of Extinction Retention and Reconsolidation Blockade by IV Allopregnanolone in PTSD.
- ClinicalTrials.gov ID
- NCT07079761
- Acronym / sponsor ID
- IV Allo PTSD / 2025000693
- Conditions
- Post Traumatic Stress Disorder
- Keywords
- Trauma, Allopregnanolone, Neurosteroid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 4 Aug 2025 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 23 Jul 2025 (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.
Purpose: About 6.4% of the U.S. population suffers from posttraumatic stress disorder (PTSD). Trauma-focused psychotherapies are generally effective in PTSD, but responses vary greatly across individuals and PTSD subpopulations. Neurobiological factors impacted by life experiences, stress, and genetics can affect treatment responses. These factors can alter brain capacities needed to reprocess traumatic memories prevent them from triggering intensely distressing, disruptive, out-of-place responses.
For example, during psychotherapy for PTSD, trauma memory activation engages two competing brain processes that affect recovery: "extinction" versus "reconsolidation" of trauma-related emotional, physiological, and behavioral responses. This study tests whether a single intravenous (IV) dose of allopregnanolone (Allo) compared to placebo (which is non-active): promotes consolidation of extinction learning (sub-study 1) or blocks reconsolidation of physiological responses triggered by aversive memories (sub-study 2). The study also tests whether Allo compared to placebo affects retention of non-aversive memories.
Detailed description
Background: Allo is a neurosteroid (hormone) produced from progesterone by the brain, adrenal glands, testes, and ovaries. Production of Allo and its equally potent, structurally similar stereoisomer pregnanolone (PA) is stimulated when certain neurons in the brain are activated and when stress activates the adrenal glands. Allo and PA markedly increase effects of gamma-amino-butyric acid (GABA; an inhibitory neurotransmitter) in the brain, thereby regulating arousal and responses to stress. Allo and PA also influence processes that strengthen or weaken memories.
Basic research suggests that several factors can reduce production of Allo: exposure to chronic or extreme stress, prolonged social isolation, chronic intermittent heavy alcohol use, certain oral contraceptives, chronic use of some psychiatric medications or other substances used to manage PTSD such as nicotine, exposure to environment toxins, and genetic predisposition.
Research shows that Allo and PA production is reduced in a large subpopulation of women and men with PTSD. Reduced Allo and PA is strongly associated with PTSD severity and poor retention of extinction learning, both of which contribute to chronic PTSD. The proposed study thus will be conducted in adult men and women with chronic PTSD. Women will be studied during two distinct phases of the menstrual cycle because progesterone levels (and therefore levels of Allo and PA) change markedly across the menstrual cycle, as do problems with extinction retention.
Study Procedures: Eligible participants between 18 and 55 years of age will take part in a widely used, standardized 3-day laboratory psychophysiology paradigm during which activation of the sympathetic nervous system (fight/flight system) is monitored via small electrode patches placed on the skin. The paradigm involves startle testing on Days 1, 2 and 3. During startle testing, participants will hear sudden bursts of white noise through headphones, see colored shapes on a computer screen, and feel sudden (not painful) blasts of air to the neck. The electrodes record participants' eye blinks, skin conductance, and heart rate. The startling sounds will be about as loud as a train but last only a fraction of a second. Participants will sit quietly with their eyes open as they listen. On study Day 2, participants are randomized by "luck of the draw" or "chance" to receive either IV Allo or placebo. On study Days 2 and 3, a brief memory test also will be conducted. Blood is collected each day for measurement of Allo, PA and other neurobiological factors that may affect the potential beneficial effects of Allo. There will be a follow up phone session (about a week after the Day 3 visit/session).
Before starting the above studies, the investigators will conduct pharmacokinetic (PK) studies in a small group of individuals with PTSD to confirm that the selected IV Allo doses increase blood Allo levels as expected.
Implications: These studies may help us understand treatable factors that increase risk for chronic or treatment-resistant PTSD and PTSD-related depression. They may also tell us whether treatments that increase Allo might help prevent or treat PTSD. IV Allo (brexanolone) at much higher doses than used in this study) is currently FDA-approved for the treatment of postpartum depression, supporting the potential for this research to spur development of Allo as a new treatment for PTSD.
Study Population: About 96 individuals with PTSD (between 18-55 years of age) will be recruited to participate in these studies. Half of the women will be studied during the follicular phase of the menstrual cycle (after onset of menses) and half during the luteal phase (after ovulation). The study is being conducted at Massachusetts General Hospital, Boston, MA.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Active drug vs. placebo will be administered in two separate experiments to a population of medically healthy, non-medicated patients with PTSD stratified by sex and by menstrual phase within female sex.
| Arm | Type | Receives |
|---|---|---|
| IV Allopregnanolone (Allo) for Extinction Retention (Expt. 1) | Experimental | Behavioral: Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Drug: Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.Arm 1 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after completion of extinction training. |
| IV Placebo for Extinction Retention (Expt. 1) | Placebo comparator | Behavioral: Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Other: Matching IV PlaceboArm 2 of Expt. 1 includes women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after completion of extinction training. |
| IV Allo for Reconsolidation Blockade (Expt. 2) | Experimental | Behavioral: Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm, Drug: Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.Arm 1 of Expt. 2 will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV Allo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+). |
| IV Placebo for Reconsolidation Blockade (Expt. 2) | Placebo comparator | Behavioral: Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigm, Other: Matching IV PlaceboArm 2 of Expt. 2 will include will include women in the early follicular or mid-luteal phase of the menstrual cycle and men with PTSD who receive IV placebo immediately after reactivation of the conditioned aversive memory by exposure to one conditioned stimulus (CS+). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Between the ages of 18 and 55 (at time of enrollment), reproductively mature, and English speaking.
- Meet criteria for chronic PTSD (i.e., CAPS-5 determined PTSD duration more than 3 months).
- Generally healthy and not on any prohibited medications (that could affect study outcomes).
- Willing to abstain from alcohol for 2 weeks and from nicotine, marijuana or illicit drugs for 4 weeks before experimental procedures and throughout the study.
- For biological females:
Key exclusion criteria (23 listed)
- Present an imminent risk to self or others or require clinical intervention to maintain safety
- Diagnosis of moderate or severe substance use disorder within three months of screening per administration of the DIAMOND substance abuse evaluation. Diagnosis of a mild substance use disorder within three months of screening will be allowed if the participant agrees to abstain from illicit drugs for one month and/or alcohol for 2 weeks prior to the experimental procedures, has a negative screening or follow-up urine toxicology and/or saliva alcohol test (if the screening test is positive), and tests negative for these substances on the morning of the experimental procedures.
- Bipolar I disorder, schizophreniform disorders, or clinically significant psychotic symptoms apart from the presence of trauma-related sensory hallucinations or negative beliefs.
- History of a suicide attempt within 1 year of enrolling.
- A history of severe TBI is exclusionary for the PK-1 and PK-2 studies. A history of moderate or severe TBI is exclusionary for the main studies (i.e., Expt. 1 and Expt. 2).
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 |
|---|---|---|
| Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigmDay 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Extinction training will occur followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on extinction retention as well as reinstatement of conditioned psychophysiological reactions will be assessed. | Behavioural | IV Allopregnanolone (Allo) for Extinction Retention (Expt. 1) |
| Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.Also: U.S. P. equivalent: brexanolone (SAGE Therapeutics) (IV Allopregnanolone with Captisol)On Day 2 of Experiment 1, a 1.7 mcg/kg dose of IV Allo will be administered over 5 minutes at the completion of extinction training to raise resting plasma Allo plus pregnanolone (PA) levels by 1500 pg/ml. This will be followed by a 4-5-hour continuous infusion of IV Allo at 2.6 mcg/kg/hr to maintain resting plasma Allo levels at the target level. | Drug | IV Allopregnanolone (Allo) for Extinction Retention (Expt. 1) |
| Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigmDay 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Extinction training will occur followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on extinction retention as well as reinstatement of conditioned psychophysiological reactions will be assessed. | Behavioural | IV Placebo for Extinction Retention (Expt. 1) |
| Matching IV PlaceboAlso: 6% USP Dexolve alone in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.On Day 2 of Experiment 1, participants randomized to placebo will receive IV matching placebo over 5 minutes at the completion of extinction training followed by a continuous infusion of matching placebo over the next 4-5 hours. The matching IV placebo will be administered according to the same per kg dosing regimen as that for active drug. | Other | IV Placebo for Extinction Retention (Expt. 1) |
| Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigmDay 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Brief exposure to the conditioned stimulus will be followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on reconsolidation blockade and reinstatement of conditioned psychophysiological reactions will be assessed. | Behavioural | IV Allo for Reconsolidation Blockade (Expt. 2) |
| Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.Also: U.S. P. equivalent: brexanolone (SAGE Therapeutics) (IV Allopregnanolone with Captisol)On Day 2 of Experiment 2, a 28 mcg/kg dose of IV Allo will be infused over 30 minutes following brief reactivation of aversively conditioned psychophysiological reactions, after which IV fluid only (0.9% normal saline) will be administered over 4-5 hours. | Drug | IV Allo for Reconsolidation Blockade (Expt. 2) |
| Experiment 2. Three-day aversive conditioning, reconsolidation blockade, and testing paradigmDay 1: Aversive conditioning will involve the pairing of a brief, noxious but not painful air blast to the neck (unconditioned stimulus; US) to a colored shape appearing on a computer monitor (conditioned stimulus). An auditory stimulus will serve as the startle probe. Day 2: Brief exposure to the conditioned stimulus will be followed by IV Allo administration. Day 3: The effects of IV Allo (administered on Day 2) on reconsolidation blockade and reinstatement of conditioned psychophysiological reactions will be assessed. | Behavioural | IV Placebo for Reconsolidation Blockade (Expt. 2) |
| Matching IV PlaceboAlso: 6% USP Dexolve alone in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer.On Day 2 of Experiment 2, matching IV placebo will be infused over 30 minutes following brief reactivation of aversively conditioned psychophysiological reactions, after which IV fluid only (0.9% normal saline) will be administered over the 4-5 hours. The matching IV placebo will be administered according to the same per kg dosing regimen as that for active drug. | Other | IV Placebo for Reconsolidation Blockade (Expt. 2) |
Primary outcome
Experiment 1: Extinction retention
Time frame: Day 3
Extinction retention is calculated as a) the difference between the average skin conductance response (SCR) to the first 4 aversively conditioned stimulus (CS+) trials and the average SCR to first 4 neutral conditioned stimulus (CS-) trials on Day 3 minus b) the difference between the average SCR to the last 4 CS+ trials and last 4 CS- trials on Day 2.
Experiment 2: Reconsolidation blockade
Time frame: Day 3
Reconsolidation blockade will be assessed by calculating the average fear potentiated startle (FPS) response to the first 4 CS+ trials on Day 3. Lower scores indicate better reconsolidation blockade.
4 secondary outcomes
Experiment 1: Reinstatement of conditioned fear
Time frame: Day 3
Experiment 2: Reinstatement of conditioned fear
Time frame: Day 3
Reinstatement of Conditioned Fear in Expt. 1
Time frame: Day 3
Reinstatement of Conditioned Fear in Expt. 2
Time frame: Day 3
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 5 Nov 2025.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Experiment 1: Three-day aversive conditioning, extinction, and extinction retention testing paradigm, Allopregnanolone (Allo) with 6% USP Dexolve (sulfobutyl ether-beta-cyclodextrin sodium salt) in 0.9% saline for IV infusion will be provided by the University of California, Davis, GMP manufacturer. and Experiment 1. Three-day aversive conditioning, extinction, and extinction retention testing paradigm in people with Post Traumatic Stress Disorder, run by Massachusetts General Hospital 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 7 inclusion and 23 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 5 Nov 2025. 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. 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 Kristen Curran ((617) 726-8508, kcurran0@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Experiment 1: Extinction retention (time frame: Day 3). 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 5 Nov 2025.