Please select the eligibility criteria that correspond to the clinical trial below.
Title: NMDA Receptor Modulation for Hyperarousal in PTSD
Brief Summary: This Phase 1b study examines the safety and efficacy of parenterally-administered lanicemine in a parallel-arm, randomized, double-blind, placebo-controlled trial in adult patients (N=24) with significant PTSD symptoms and elevated anxiety potentiated startle (APS). Investigator hypothesize that lanicemine (100 mg) displays a normalization of APS following three infusions over 5 non-consecutive days. If target engagement is demonstrated and the drug is safe and tolerable in this patient population, investigator will proceed to a larger POC study.


Options:
A: Inclusion Criteria:

* Adults survivors of traumatic events

Exclusion Criteria:

* Traumatic brain injury
* Lifetime psychosis
* Life time (prior) PTSD
* Medical conditions forbidding SSRIs
B: Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Patients must provide acceptable proof of identity documentation to confirm initials and date of birth
3. Male and female patients aged 21 to 65 years, inclusive.
4. All male patients who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of IP until 12 weeks after their last dose. All females must have a negative serum pregnancy test. Women of childbearing potential (WOCBP, see below) must use a highly effective form of birth control plus the use of a condom by the male sexual partner, reviewed and approved by the PI. The highly effective form of birth control includes: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective IUD/IUS, Depo-Provera injections, oral contraceptive, and Evra Patch or Nuvaring. Women should be on a stable method of birth control for a minimum of 3 months , prior to randomization and 3 months after the last dose of IP.

   Women of non-childbearing potential. Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they are amenorrheic for 12 months prior to randomization without an alternative medical cause. The following age-specific requirements apply:

   Women \< 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.

   Women ≥ 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
5. CAPS-5 score ≥ 25 and CGI-S ≥ 4 at Screening and Randomization
6. Anxiety Potentiated Startle T-score ≥ 2.8.
7. Psychotropic medications must remain at a stable dose for at least 42 days prior to screening, without clinically significant adjustment.
8. Be able to understand and comply with the requirements of the study, as judged by the investigator

Exclusion Criteria:

1. Patients who are currently participating in another clinical study in which the patient is exposed to an investigational or non-investigational drug or device, or have done so within the last 30 days prior to screening.
2. Patients who have no regular contact with an adult who could come to the patient's aid should an urgent need arise.
3. Patients with a history of DSM-5 diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder, or currently exhibiting psychotic symptoms associated with depression; dementia or suspicion thereof, is also exclusionary.
4. Currently being treated with MAOIs, lithium, divalproex, carbamazepine, barbiturates, or benzodiazepines. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[eg, riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine\], or the mu-opioid receptor.
5. Patients who meet DSM-5 criteria for substance use disorder (amphetamines, cocaine, hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within 1 month prior to screening. Patients with a positive urine drug screen (UDS) are excluded except for patients testing positive for prescribed medications that are otherwise permitted and there is no evidence of misuse or abuse. Patients can be re-tested only if either the initial opiate or barbiturate result is positive and they have a prescription, but the patient should be excluded if the result is still positive at the second test. Patients with positive UDS for drug(s) legally available by prescription must provide evidence of prescription for the drug(s).
6. Patients with a binge-pattern of alcohol use which makes them at risk for withdrawal-related seizures. Also, significant alcohol withdrawal symptoms that require medical detoxification.
7. Patients with a suicide attempt within the last 3 months or at imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigator.
8. Patients who are pregnant or lactating.
9. Clinically significant laboratory value, physical examination, or ECG that signifies a major medical illness that is unstable or inadequately controlled, or that may put the subject at risk during the study in the judgment of the investigator. Hypothyroidism is permitted if corrected and the patient is on a stable treatment regimen for a minimum of 6 months.
10. Systolic BP \< 85 or \> 160 mmHg or diastolic BP \> 100 mmHg or heart rate \< 50 or \>105 beats per minute at Screening or Randomization. Exclusionary values may be repeated once.
11. QTcF (Fridericia-corrected) ≥ 450 msec at Screening or Randomization. Exclusionary values may be repeated once.
12. Patients with any history of seizure disorder (except for febrile seizures in childhood) or traumatic brain injury.
13. Previous exposure to lanicemine.
14. Patients with a personality disorder which in the opinion of the investigator has a major impact on the patient's current psychiatric status and would preclude safe study participation.
15. Body mass index (BMI) ≥ 40 kg/m2
C: Inclusion Criteria:

* Third-trimester pregnant women being followed at the Massachusetts General Hospital (MGH) Obstetrics Program
* At risk of postpartum depression (PPD)

Exclusion Criteria:

* Failure to participate in regular prenatal check-ups
* Current diagnosis Diagnostic and Statistical Manual of Mental Disorders (DSM-5) mental disorder pertaining to psychosis or substance abuse
* Suicidality
* Obstetric complication (e.g., preeclampsia, excessive hemorrhaging)
* Use of potentially confounding or interacting medications
* Complicating pediatric medical condition in the newborn
D: Inclusion Criteria:

1. Clinical evidence of infection within the previous 72 hours (may be present longer than 72 hours) (a, b, c, or d - only 1 required)

   1. Presence of polymorphonuclear cells in a normally sterile body fluid (excluding blood);
   2. Culture or Gram stain of blood, sputum, urine or normally sterile body fluid positive for a pathogenic micro-organism;
   3. Focus of infection identified by visual inspection (e.g. ruptured bowel with the presence of free air or bowel contents in the abdomen found at the time of surgery, wound with purulent drainage);
   4. Other clinical evidence of infection - treated community acquired pneumonia, purpura fulminans, necrotising fascitis, etc.
2. Evidence of a systemic response to infection as defined by the presence of two or more of the following signs within the previous 24 hours. These signs may be present longer than 72 hours.

   1. Fever (temperature \>38.3°C) or hypothermia (rectal temperature \< 35.6°C);
   2. Tachycardia (heart rate of \>90 beat/min);
   3. Tachypnea (respiratory rate \> 20 breaths/min, PaC02\<32 mmHg) or patient requires invasive mechanical ventilation;
   4. Alteration of the WBC count \>12,000 cells/mm3, \<4,000 cells/mm3 or \>10% immature neutrophils (bands).
3. Evidence of shock defined by (A + B- both required within the previous 72 hours (may NOT be present longer than 72 hours).

A. A systolic blood pressure \< 90 mmHg or a decrease in SBP of more than 50 mmHg from baseline in previous hypertensive patients (for at least one hour) despite adequate fluid replacement OR need for vasopressors for at least one hour (infusion of dopamine ≥ 5 mcg/kg/min or any dose of adrenaline, noradrenaline, phenylephrine or vasopressin) to maintain a SBP ≥ 90 mmHg;

B. Hypoperfusion or organ dysfunction which is not the result of underlying diseases or drugs, but is attributable to sepsis, including one of the following:

1. Sustained oliguria (urine output \< 0.5 ml/kg/hr for a minimum of 1 hour)
2. Metabolic acidosis \[pH of \< 7.3, or a base deficit of \> or = 5.0 mmol/L, or an increased lactic acid concentration (\> 2 mmol/L)\].
3. Arterial hypoxemia (Pa02/FI02\<280 in the absence of pneumonia)(Pa02/FI02\<200 in the presence of pneumonia).
4. Thrombocytopenia - platelet count ≤ 100,000 cells/mm3.
5. Acute altered mental status (Glasgow Coma Scale \< 14 or acute change from baseline).

4. Informed Consent

5. Cortisol level at baseline and 60 minutes after 0.25 mg cosyntropin

Exclusion Criteria:

1. Pregnancy
2. Age less than 18.
3. Underlying disease with a prognosis for survival of less than 3 months.
4. Cardiopulmonary resuscitation within 72 hours before study.
5. Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4 weeks before the study.
6. Administration of chronic corticosteroids in the last 6 months or acute steroid therapy (any dose) within 4 weeks (including inhaled steroids). Topical steroids are not exclusions.
7. HIV positivity.
8. Presence of an advanced directive to withhold or withdraw life sustaining treatment (i.e. DNR).
9. Advanced cancer with a life expectancy less than 3 months.
10. Acute myocardial infarction or pulmonary embolus.
11. Another experimental drug study within the last 30 days.
12. Moribund patients likely to die within 24 hours.
13. Patients in the ICU for more than 2 months at the time of the start of septic shock.

Answer: B