DepressionPhase 1NCT03166501
NMDA Receptor Modulation for Hyperarousal in PTSD
A Phase 1 study testing Lanicemine in people with Depression and Post Traumatic Stress Disorder, run by Baylor College of Medicine at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Depression, Post Traumatic Stress Disorder
- What is being tested?
- Lanicemine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2018to 14 Nov 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Patients must provide acceptable proof of identity documentation to confirm initials and date of birth
- Male and female patients aged 21 to 65 years, inclusive.
- 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.
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- 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.
- CAPS-5 score ≥ 25 and CGI-S ≥ 4 at Screening and Randomization
- Anxiety Potentiated Startle T-score ≥ 2.8.
- Psychotropic medications must remain at a stable dose for at least 42 days prior to screening, without clinically significant adjustment.
- Be able to understand and comply with the requirements of the study, as judged by the investigator
Who cannot join
- 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.
- Patients who have no regular contact with an adult who could come to the patient's aid should an urgent need arise.
- 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.
- 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.
- 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).
- 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.
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- 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.
- Patients who are pregnant or lactating.
- 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.
- 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.
- QTcF (Fridericia-corrected) ≥ 450 msec at Screening or Randomization. Exclusionary values may be repeated once.
- Patients with any history of seizure disorder (except for febrile seizures in childhood) or traumatic brain injury.
- Previous exposure to lanicemine.
- 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.
- Body mass index (BMI) ≥ 40 kg/m2
Trial locations and contacts
1 site in 1 country.
United States1 site
Michael E. DeBakey VA Medical Center
Houston, Texas, 77030
About this study
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.
Read the detailed description
This study aims to provide a rigorous test of functional target engagement and "go/no go" milestones for a subsequent POC trial. Investigator will conduct a parallel-arm, randomized, double-blind, placebo-controlled study to assess lanicemine (100 mg) with respect to a functional pharmacodynamic readout of target engagement (APS). Twenty-four patients with significant PTSD symptoms and elevated APS will be randomized to one of 2 treatment groups [placebo or 100 mg], and undergo three 60 min parenteral infusions over a 5 day period. APS and other neurophysiological biomarkers will be tested before and after the 1st and 3rd treatment.
Primary Objective is to examine, relative to placebo, whether lanicemine will demonstrate normalization of the APS response following three treatments.
Secondary Objectives are to examine, relative to placebo, whether lanicemine will demonstrate effects on P50 auditory evoked potentials, gamma band EEG, and Mismatch Negativity. Investigator also explore whether target engagement will mediate the effect of treatment on CAPS-5 scores.
- Conditions
- Depression, Post Traumatic Stress Disorder
- Being tested
- Lanicemine, Placebo
- Medical subject headings
- Depression, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LanicemineDrug
Also called BHV-5500
Three 60 min parenteral infusions over a 5 day period
PlaceboDrug
Also called Baxter
Three 60 min parenteral infusions over a 5 day period
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Lanicemine 100mg Intravenous Receives: Drug: Lanicemine |
| Placebo | Placebo comparator | Normal saline Intravenous Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Objective
Primary Objective is to examine, relative to placebo, whether lanicemine will demonstrate normalization of the APS response following three treatments.
Measured: 24 months
Secondary outcomes (4)
Secondary Objectives (1/4)
To examine, relative to placebo, whether lanicemine will demonstrate effects on P50 auditory evoked potentials
Measured: 24 months
Secondary Objectives (2/4)
To examine, relative to placebo, whether lanicemine will demonstrate effects on gamma band EEG
Measured: 24 months
Secondary Objectives (3/3)
To examine, relative to placebo, whether lanicemine will demonstrate effects on Mismatch Negativity
Measured: 24 months
Secondary Objectives (4/4)
Also explore whether target engagement will mediate the effect of treatment on CAPS-5 scores.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start1 Sep 2018
- Primary completion12 Nov 2019
- Study completion14 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Sanjay Johan Mathew, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03166501
- Sponsor's protocol ID
- 36371
- Other IDs
- 1R61MH110540-01
- Status last verified
- Nov 2019
- First submitted
- 23 May 2017
- Last updated
- 19 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.
PubMed 38767196Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.
PubMed 35141873Ramakrishnan N, Lijffijt M, Green CE, Balderston NL, Murphy N, Grillon C, Iqbal T, Vo-Le B, O'Brien B, Murrough JW, Swann AC, Mathew SJ. Neurophysiological and clinical effects of the NMDA receptor antagonist lanicemine (BHV-5500) in PTSD: A randomized, double-blind, placebo-controlled trial. Depress Anxiety. 2021 Nov;38(11):1108-1119. doi: 10.1002/da.23194. Epub 2021 Jul 12.
PubMed 34254405Murphy N, Lijffijt M, Ramakrishnan N, Vo-Le B, Vo-Le B, Iqbal S, Iqbal T, O'Brien B, Smith MA, Swann AC, Mathew SJ. Does mismatch negativity have utility for NMDA receptor drug development in depression? Braz J Psychiatry. 2022 Jan-Feb;44(1):61-73. doi: 10.1590/1516-4446-2020-1685.
PubMed 33825765Lijffijt M, Green CE, Balderston N, Iqbal T, Atkinson M, Vo-Le B, Vo-Le B, O'Brien B, Grillon C, Swann AC, Mathew SJ. A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD. Front Psychiatry. 2019 Dec 13;10:846. doi: 10.3389/fpsyt.2019.00846. eCollection 2019.
PubMed 31920733
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NMDA Receptor Modulation for Hyperarousal in PTSD
- ClinicalTrials.gov ID
- NCT03166501
- Acronym / sponsor ID
- 36371
- Conditions
- Depression, Post Traumatic Stress Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 12 Nov 2019 (actual)
- Study completion
- 14 Nov 2019 (actual)
- First posted
- 25 May 2017 (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.
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.
Detailed description
This study aims to provide a rigorous test of functional target engagement and "go/no go" milestones for a subsequent POC trial. Investigator will conduct a parallel-arm, randomized, double-blind, placebo-controlled study to assess lanicemine (100 mg) with respect to a functional pharmacodynamic readout of target engagement (APS). Twenty-four patients with significant PTSD symptoms and elevated APS will be randomized to one of 2 treatment groups [placebo or 100 mg], and undergo three 60 min parenteral infusions over a 5 day period. APS and other neurophysiological biomarkers will be tested before and after the 1st and 3rd treatment.
Primary Objective is to examine, relative to placebo, whether lanicemine will demonstrate normalization of the APS response following three treatments.
Secondary Objectives are to examine, relative to placebo, whether lanicemine will demonstrate effects on P50 auditory evoked potentials, gamma band EEG, and Mismatch Negativity. Investigator also explore whether target engagement will mediate the effect of treatment on CAPS-5 scores.
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 |
|---|---|---|
| Treatment | Experimental | Drug: LanicemineLanicemine 100mg Intravenous |
| Placebo | Placebo comparator | Drug: PlaceboNormal saline Intravenous |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Provision of signed and dated informed consent form
- Patients must provide acceptable proof of identity documentation to confirm initials and date of birth
- Male and female patients aged 21 to 65 years, inclusive.
- 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:
Key exclusion criteria (15 listed)
- 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.
- Patients who have no regular contact with an adult who could come to the patient's aid should an urgent need arise.
- 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.
- 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.
- 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).
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 |
|---|---|---|
| LanicemineAlso: BHV-5500Three 60 min parenteral infusions over a 5 day period | Drug | Treatment |
| PlaceboAlso: BaxterThree 60 min parenteral infusions over a 5 day period | Drug | Placebo |
Primary outcome
Primary Objective
Time frame: 24 months
Primary Objective is to examine, relative to placebo, whether lanicemine will demonstrate normalization of the APS response following three treatments.
4 secondary outcomes
Secondary Objectives (1/4)
Time frame: 24 months
Secondary Objectives (2/4)
Time frame: 24 months
Secondary Objectives (3/3)
Time frame: 24 months
Secondary Objectives (4/4)
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Derived from this study: PubMed 38767196Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.
- Derived from this study: PubMed 35141873Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.
- Derived from this study: PubMed 34254405Ramakrishnan N, Lijffijt M, Green CE, Balderston NL, Murphy N, Grillon C, Iqbal T, Vo-Le B, O'Brien B, Murrough JW, Swann AC, Mathew SJ. Neurophysiological and clinical effects of the NMDA receptor antagonist lanicemine (BHV-5500) in PTSD: A randomized, double-blind, placebo-controlled trial. Depress Anxiety. 2021 Nov;38(11):1108-1119. doi: 10.1002/da.23194. Epub 2021 Jul 12.
- Derived from this study: PubMed 33825765Murphy N, Lijffijt M, Ramakrishnan N, Vo-Le B, Vo-Le B, Iqbal S, Iqbal T, O'Brien B, Smith MA, Swann AC, Mathew SJ. Does mismatch negativity have utility for NMDA receptor drug development in depression? Braz J Psychiatry. 2022 Jan-Feb;44(1):61-73. doi: 10.1590/1516-4446-2020-1685.
- Derived from this study: PubMed 31920733Lijffijt M, Green CE, Balderston N, Iqbal T, Atkinson M, Vo-Le B, Vo-Le B, O'Brien B, Grillon C, Swann AC, Mathew SJ. A Proof-of-Mechanism Study to Test Effects of the NMDA Receptor Antagonist Lanicemine on Behavioral Sensitization in Individuals With Symptoms of PTSD. Front Psychiatry. 2019 Dec 13;10:846. doi: 10.3389/fpsyt.2019.00846. eCollection 2019.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lanicemine in people with Depression and Post Traumatic Stress Disorder, run by Baylor College of Medicine 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 11 inclusion and 15 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: finished, as of the sponsor's last update on 19 Aug 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Objective (time frame: 24 months). 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 NCT03166501, which also lists 5 linked publications.
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 19 Aug 2020; AzTrials last refreshed its copy on 28 Oct 2026.