Target Engagement of D-cycloserine (DCS)

Major Depressive Disorder Clinical Trial

Official title:

Target Engagement of D-cycloserine (DCS)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03401164
• Other study ID #: 7427
• Status: Not yet recruiting
• Phase: Phase 2
• First received: November 27, 2017
• Last updated: January 8, 2018
• Start date: March 2018
• Est. completion date: February 28, 2020

Study information

• Verified date: January 2018
• Source: New York State Psychiatric Institute
• Contact: Joshua T Kantrowitz, MD
• Phone: 646-774-6738
• Email: Joshua.Kantrowitz[@]nyspi.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assess the mechanism of action of d-cycloserine (DCS) to guide development of other medications working via similar molecular targets.

Description:

Evaluate the target engagement of DCS with Proton magnetic resonance spectroscopy (1H MRS) measurement of glutamate and glutamine (Glx) and GABA responses to DCS. The main purpose of the study will be to look at the acute effects of DCS on 1H MRS measured glutamate and gamma- aminobutyric acid (GABA), followed by an optional follow-up four week phase of lurasidone plus DCS and an magnetic resonance imagine (MRI) at the end of this four week treatment to assess both clinical and biomarker response to the four week treatment. Using combined DCS/lurasidone has potential unique synergies, with lurasidone blocking residual risk of psychosis with DCS, and DCS blocking akathisia associated with use of lurasidone or other atypical antipsychotics, along with potential synergistic antidepressive symptoms with the combination. There is an optional 4 week treatment with DCS + lurasidone following the MRI.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: February 28, 2020
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Diagnostic and Statistical Manual-V(DSM-V) diagnosis of current major depressive episode and Montgomery-Åsberg Depression Rating Scale (MADRS) > 17

• Off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study. One exception is chloral hydrate or short acting benzodiazepines for distressing anxiety or insomnia (up to 72 hours prior to each MRI scan). In addition, patients will be off antipsychotics for 1 month and off fluoxetine for 6 weeks prior to the study

• Willing to provide informed consent

• Medically stable for study participation

• Subject is medication free at baseline or clinically judged to be likely to be able to tolerate a medication washout. Only subjects who have failed their current medication regiment will be washed off medications. A failed regiment constitutes not achieving at least partial remission after an adequate dose of antidepressant medication for at least three weeks.

Exclusion Criteria:

• Substance use disorder (excluding nicotine) within last 90 days

• History of schizophrenia, schizoaffective disorder or delusional disorder or current major depression or bipolar disorder with psychotic features or history of chronic psychosis for >50% of time

• Women will be excluded if they are pregnant, lactating, or not either surgically-sterile or using appropriate methods of birth control. Women must agree to continue using applicable birth control throughout the trial. All women of child-bearing potential must have a negative urine human chorionic gonadotropin (hCG) pregnancy test at the screening visit (1 week before beginning study)

• Taking any medication contraindicated with DCS (ethionamide, isoniazid)

• History of seizures, renal insufficiency or congestive heart failure

• Clinically abnormal liver function tests (LFTs), thyroid, renal function or anemia

• Contraindication to MRI scanning, including metal implants or claustrophobia.

• Medicinal patch, unless removed

• Active suicide or violence risk

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• D-cycloserine
D-cycloserine 1000 mg
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	NeuroRx, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute increase in glutamate + glutamine (Glx)	Compare changes in Glx response to administration of d-cycloserine (DCS) vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the Glx over creatinine ratios, with higher values indicating higher Glx/creatinine ratios.	At least 1 day between the two scans
Secondary	Acute increase in gamma- aminobutyric acid (GABA)	Compare changes in GABA response to administration of DCS vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the GABA over creatinine ratios, with higher values indicating higher GABA/creatinine ratios.	At least 1 day between the two scans
Secondary	Hamilton Depression Rating Scale (HAM-D)	Depression rating scale: Range 0-53, higher scores indicate worse depression. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression; = 23 = Very Severe Depression	4 weeks