Pharmacokinetic Study, Post Traumatic Stress Disorder
Conditions
Keywords
Pharmacokinetic study, Allopregnanolone (Allo), Vital signs, Sedation ratings, Pulse oximeter data
Brief summary
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 to prevent them from triggering intense, distressing, disruptive, out-of-place responses. Before starting the interventional study (described in detail in NCT07079761), the investigators will conduct two pharmacokinetic (PK) studies (PK-1 and PK-2) in a small group of individuals with PTSD to test dosing and safety at Boston Medical Center.
Interventions
DRUGPK-1 Good Manufacturing Practices (GMP) allopregnanolone (Allo) with Dexolve in 0.9% saline for infusion manufactured by the University of California, Davis
For the PK-1 group, after the 5-minute loading dose of IV allopregnanolone, the dose was changed as prescribed to optimize the subject's target plasma allopregnanolone + pregnanolone level for the next 4-5 hours.
DRUGPK-2 GMP allopregnanolone (Allo) with Dexolve in 0.9% saline for infusion manufactured by the University of California, Davis.
For the PK-2 group, after the 30-minute drug infusion of IV allopregnanolone, the IV allopregnanolone was discontinued and only normal saline was continued for the next 4-5 hours.
Sponsors
Boston University
National Institute of Mental Health (NIMH)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Masking description
These pharmacokinetic (PK) studies are open-label studies confirming the dosing and safety of dosing for the main studies in NCT07079761.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Chronic Posttraumatic Stress Disorder * 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 * Females: must have a menstrual cycle and not be on hormonal birth control (with a few exceptions; see below) * If gender non-conforming: must not be on hormone therapy
Exclusion criteria
* Bipolar I disorder, schizophreniform disorder, or clinically significant psychotic symptoms apart from the presence of trauma-related sensory hallucinations or negative beliefs * Moderate or severe substance use disorder within three months of screening * Sleep Apnea * History of a suicide attempt within 1 year of enrolling * Imminent risk to self or others or requiring clinical intervention to maintain safety * Unstable medical condition or condition that may affect outcomes * Moderate or severe traumatic brain injury (TBI) (mild TBI acceptable; moderate TBI allowed for PK study) * Using any medications or substances (per self-report or toxicology testing) that may increase the risk for IV Allo side effects or affect the experimental results. * Unable to tolerate IV placement or blood drawing by needle stick * Wear hearing aids or fail hearing test (not applicable to PK study) * Females: pregnant, breastfeeding, or if of childbearing potential, unwilling to use two forms of effective birth control \[except for hormonal contraceptives, unless intrauterine device (IUD) or a device like NuvaRing\] for one week before and one month after study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Assessed Sedation Levels for Each Participant | resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes | Sedation levels will be assessed with the Qualitative Sedation Rating Scale. It has 5 categories: None- responds normally to verbal commands, cognitive \& coordination not impaired, ventilatory \& cardiovascular functions unaffected; Minimal- responds normally to verbal commands, unaffected ventilatory \& cardiovascular functions, mild feelings of intoxication, cognitive function \& coordination may be impaired; Moderate-responds purposefully to commands alone or with light touch, protective airway reflexes \& adequate ventilation maintained without intervention, cardiovascular function remains stable; Deep- cannot be easily aroused but responds purposefully to noxious stimulation, assistance may be needed to ensure the airway is protected \& adequate ventilation maintained, cardiovascular function is usually stable; Dissociative- trance-like cataleptic state with profound analgesia \& amnesia, airway protective reflexes, spontaneous respirations \& cardiopulmonary stability retained. |
| Blood Oxygen Saturation | resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes | Average across participants of blood oxygen saturation levels obtained via pulse oximetry (ranging from 0% to 100%) for each time point indicated. |
| Respiratory Rate | resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes | Average across participants of respiratory rate for each time point indicated. |
| Pulse Rate | resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes | Average across participants of pulse rate for each time point indicated. |
| Diastolic Blood Pressure | resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes | Average across participants of diastolic blood pressure for each time point indicated. |
| Systolic Blood Pressure | resting pre-infusion; after loading dose at 0 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 300 minutes | Average across participants of systolic blood pressure for each time point indicated. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAnn M Rasmusson, MD
Boston University Chobanian & Avedisian School of Medicine, Dept of Psychiatry
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
None listed