Major Depressive DisorderPhase 2NCT02695472
Study of NSI-189 for Major Depressive Disorder
A Phase 2 study testing 80 Milligrams NSI-189 and 40 Milligrams NSI-189 in people with Major Depressive Disorder, run by Neuralstem Inc. at 13 sites in United States.
Trial summary
The study will consist of a screening period and a randomized treatment. Approximately 220 subjects who meet eligibility during the screening period will be randomized to initiate a 12-week, double-blind treatment with NSI-189 80 milligrams/day (provided as 40 milligrams twice per day), NSI-189 40 milligrams once a… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- 80 Milligrams NSI-189 and 40 Milligrams NSI-189
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 13 sitesUnited States
- Study dates
- Mar 2016to Dec 2017
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subject has the ability to understand the purpose, potential benefits and risks of the study and to provide signed and dated informed consent, authorizing the use of protected health information in accordance with national and local Subject privacy regulations.
- Males and females 18 to 60 years of age, inclusive, at the time of informed consent.
- Diagnosis of major depressive disorder, recurrent, as per Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and confirmed by Structured Clinical Interview for the Diagnostic and Statistical Manual specific for Clinical Trials. Their major depressive episode must be at least 8 weeks in duration and confirmed via Structured Clinical Interview for the Diagnostic and Statistical Manual mood module interview administered by a remote, independent raters, prior to the baseline visit.
- Montgomery-Asberg Depression Scale (MADRS) score of 20 or greater, at Screening and Baseline (MADRS score confirmed to be 20 or greater via remote SAFER interview by an independent rater prior to the baseline visit).
- The following applies to female Subjects: Non-pregnant, non-lactating females of childbearing potential are eligible as long as they agree to use a double barrier method of birth control from Screening until 3 months following discontinuation of IP. Women who are not of childbearing potential (bilateral oophorectomy, bilateral tubal ligation, hysterectomy, or post-menopausal for at least 1 year) will not require such parameters in order to be eligible.
- The following applies to male subjects: Male subjects with a female partner of childbearing potential will be required to use double barrier method of birth control or practice abstinence during this study and for 3 months following discontinuation of Investigational Product. Note: These requirements also apply for male subjects who have had a vasectomy.
- Body mass index (BMI) ≥19.5 and ≤38.0 kg/m2, at Screening. Bodyweight must be >50 kg.
- Of stable medical health, in the opinion of the Site Investigator, as determined by Investigator discretion (medical history, physical examination, vital signs, ECG, and clinical laboratory assessments).
Who cannot join
- Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or other major disease as determined by the Investigator or designee such that participation in the study would place subjects at increased risk for serious adverse events.
- History of cancer or malignancy within the last 5 years. Note: Subjects with basal or squamous cell carcinoma may be permitted into the study on a case by case basis.
- History of seizures; head trauma; or any clinically significant finding on the neurologic examination such that participation in the study would place subjects at increased risk for serious adverse events.
- Previous or current diagnosis of bipolar or schizoaffective disorder or psychotic disorder, or any psychotic symptoms during the current major depressive episode (according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition).
- Subjects who have a concurrent primary psychiatric diagnosis, diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th edition, other than depression.
- Subjects with delirium, dementia, Parkinson's disease, or Huntington's disease.
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- Subjects who have failed to respond to more than two antidepressant trials of adequate dose (as defined in Massachusetts General Hospital Antidepressant Treatment Response) and duration (at least 8 weeks in duration) during the current major depressive episode as determined by the local rater and confirmed by an independent, remote rater prior to the baseline visit.
- Subjects with clinically significant suicidal ideation and/or behavior currently as determined by the Site Investigator, such that participation in the study would place subjects at increased risk for serious adverse events.
- Subjects with any current homicidal ideation.
- Clinically significant abnormal clinical chemistry values, as determined by the Site Investigator, or any values for Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), total bilirubin or creatinine that are 1.5 times above the upper limit of normal (ULN) and deemed clinically significant by the Site Investigator; any clinically significant values as determined by the Site Investigator for platelets or hemoglobin that are below the lower limit of normal (LLN); or any out of normal range values for white blood cells (WBC) deemed clinically significant by the Site Investigator.
- Clinically significant (as determined by the Investigator) 12-lead Electrocardiogram (ECG) abnormalities, including corrected QT interval using Bazett's correction method of >450 msec for males and >470 msec for females.
- Subjects with (current) severe Post-Traumatic Stress Disorder (PTSD), severe Obsessive Compulsive Disorder (OCD), severe binge eating disorder, or subjects with anorexia or bulimia nervosa active within the past three years.
- Subjects who plan to undergo elective invasive procedures/surgeries at any time during the study through End-of-study.
- Subjects taking excluded medications (See Appendix 1)..
- History of alcohol or drug-dependence or abuse by Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and confirmed by Structured Clinical Interview for the Diagnostic and Statistical Manual specific for Clinical Trials within 12 months prior to Screening.
- Positive screening test or baseline test for drugs-of-abuse (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, phencyclidine). Note any positive test result(s) for benzodiazepine(s), opiates, or psychostimulants accompanied by confirmation of a prescription for a valid medical reason will be allowed.
- Positive serum β-human chorionic gonadotropin (β-HCG) test at Screening or positive urine pregnancy test at baseline that is consistent with pregnancy (females only).
- Donation or loss of whole blood >200 mL within 30 days prior to dosing or ≥500 mL within 56 days prior to dosing. Note: Blood taken for routine medical evaluations totaling less than 50 mL will be permitted.
- Females who are pregnant, lactating, or planning to become pregnant during the study.
- Does not tolerate venipuncture.
- Subjects who have had electroconvulsive therapy within the 6 months prior to Screening.
- Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an Investigational Product or approved therapy for investigational use within 45 days (or 5 half-lives, whichever is longer) prior to Day 1 of Investigational Product administration.
- Any concurrent disease or condition that, in the opinion of the Investigator, would make the subject unsuitable for participation in the clinical study.
- Subject who, in the opinion of the Site Investigator, are unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope and possible consequences of the clinical study.
- Subject who, in the opinion of the Site Investigator, are unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude, inability to return for follow-up and improbability of completing the clinical study.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Institute for Advanced Medical Research
Alpharetta, Georgia, 30005
FutureSearch Trials of Dallas
Dallas, Texas, 75231
Midwest Clinical Research Center, LLC
Dayton, Ohio, 45417
Clinical Trials of the Rockies
Denver, Colorado, 80209
Collaborative Neuroscience Network, LLC
Garden Grove, California, 92845
Clinical Neuroscience Solutions, Inc.
Jacksonville, Florida, 32256
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, 38119
Synergy San Diego
National City, California, 91950
Clinical Neuroscience Solutions, Inc
Orlando, Florida, 32801
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Psychiatric Medicine Associates, LLC
Skokie, Illinois, 60076
St. Louis Clinical Trials, LC
St Louis, Missouri, 63141
Richmond Behavioral Associates
Staten Island, New York, 10312
About this study
Official title: A Phase 2, Double-Blind, Placebo-Controlled Study of NSI-189, a Neurogenic Compound Among Out-Patients With Major Depressive Disorder
The study will consist of a screening period and a randomized treatment. Approximately 220 subjects who meet eligibility during the screening period will be randomized to initiate a 12-week, double-blind treatment with NSI-189 80 milligrams/day (provided as 40 milligrams twice per day), NSI-189 40 milligrams once a day, or placebo.
Read the detailed description
The screening period will range from a minimum of 14 days to a maximum of 28 days. The Investigators will determine that the subjects meet eligibility criteria and will collect the demographic and medical data permitting full characterization of the subject.
The duration of the randomization period will be 12 weeks. Subjects who meet inclusion/exclusion criteria at the Baseline Visit will be randomized to NSI-189 80 milligrams/day, given as 40 milligrams twice per day, NSI-189 40 milligrams/day, given once a day, or placebo. The treatment will be double-blinded.
- Conditions
- Major Depressive Disorder
- Being tested
- 80 Milligrams NSI-189, Placebo, 40 Milligrams NSI-189
- Keywords
- Depression, Major Depressive Disorder (MDD), Major Depressive Disorder, Neurogenesis, Synaptogenesis, NSI-189, Neuralstem
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
80 Milligrams NSI-189Drug
Also called NSI-189 twice per day (BID)
Orally Administered
PlaceboDrug
Orally administered
40 Milligrams NSI-189Drug
Also called NSI-189 Once a day (QD)
Orally Administered
| Study group | Role | What they receive |
|---|---|---|
| Placebo Arm | Placebo comparator | One Placebo tablet, twice daily Receives: Drug: Placebo |
| 40 Milligrams NSI-189, total dose daily | Experimental | One 40 Milligrams NSI-189 tablet and 1 placebo tablet per day Receives: Drug: Placebo; Drug: 40 Milligrams NSI-189 |
| 80 Milligrams NSI-189, total dose daily | Experimental | One 40 Milligrams NSI-189 tablet twice per day Receives: Drug: 80 Milligrams NSI-189 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS)
Measured: Up to 12 weeks
Secondary outcomes (6)
Symptoms of Depression Questionnaire (SDQ)
Measured: Up to 12 weeks
The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ)
Measured: Up to 12 weeks
17-item Hamilton Rating Scale for Depression (HAMD17)
Measured: Up to 12 weeks
Clinical Global Impressions - Severity and Improvement (CGI-S, CGI-I)
Measured: Up to 12 weeks
Cogstate Brief Battery
A computerized battery used to measure psychomotor, attention, learning and working memory performance. The subject results are compared with normative data from a population with similar age and gender.
Measured: Up to 12 weeks
CogScreen
A computerized battery focused on measures of attention, concentration, information processing, memory span, and working memory. The subject results are compared with normative data from a population with similar age and gender.
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionJun 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuralstem Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Karl Johe, Ph.D., Study director, Neuralstem Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02695472
- Sponsor's protocol ID
- NS2014-1
- Status last verified
- Feb 2017
- First submitted
- 15 Feb 2016
- Last updated
- 24 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Fava M, Johe K, Ereshefsky L, Gertsik LG, English BA, Bilello JA, Thurmond LM, Johnstone J, Dickerson BC, Makris N, Hoeppner BB, Flynn M, Mischoulon D, Kinrys G, Freeman MP. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2016 Oct;21(10):1372-80. doi: 10.1038/mp.2015.178. Epub 2015 Dec 8.
PubMed 26643541Tajiri N, Quach DM, Kaneko Y, Wu S, Lee D, Lam T, Hayama KL, Hazel TG, Johe K, Wu MC, Borlongan CV. NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats. J Cell Physiol. 2017 Oct;232(10):2731-2740. doi: 10.1002/jcp.25847. Epub 2017 Apr 25.
PubMed 28181668
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Placebo-Controlled Study of NSI-189, a Neurogenic Compound Among Out-Patients With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT02695472
- Acronym / sponsor ID
- NS2014-1
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, Major Depressive Disorder (MDD), Major Depressive Disorder, Neurogenesis, Synaptogenesis, NSI-189, Neuralstem
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Neuralstem Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 1 Mar 2016 (estimated)
- 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.
The study will consist of a screening period and a randomized treatment. Approximately 220 subjects who meet eligibility during the screening period will be randomized to initiate a 12-week, double-blind treatment with NSI-189 80 milligrams/day (provided as 40 milligrams twice per day), NSI-189 40 milligrams once a day, or placebo.
Detailed description
The screening period will range from a minimum of 14 days to a maximum of 28 days. The Investigators will determine that the subjects meet eligibility criteria and will collect the demographic and medical data permitting full characterization of the subject.
The duration of the randomization period will be 12 weeks. Subjects who meet inclusion/exclusion criteria at the Baseline Visit will be randomized to NSI-189 80 milligrams/day, given as 40 milligrams twice per day, NSI-189 40 milligrams/day, given once a day, or placebo. The treatment will be double-blinded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo Arm | Placebo comparator | Drug: PlaceboOne Placebo tablet, twice daily |
| 40 Milligrams NSI-189, total dose daily | Experimental | Drug: Placebo, Drug: 40 Milligrams NSI-189One 40 Milligrams NSI-189 tablet and 1 placebo tablet per day |
| 80 Milligrams NSI-189, total dose daily | Experimental | Drug: 80 Milligrams NSI-189One 40 Milligrams NSI-189 tablet twice per day |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subject has the ability to understand the purpose, potential benefits and risks of the study and to provide signed and dated informed consent, authorizing the use of protected health information in accordance with national and local Subject privacy regulations.
- Males and females 18 to 60 years of age, inclusive, at the time of informed consent.
- Diagnosis of major depressive disorder, recurrent, as per Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and confirmed by Structured Clinical Interview for the Diagnostic and Statistical Manual specific for Clinical Trials. Their major depressive episode must be at least 8 weeks in duration and confirmed via Structured Clinical Interview for the Diagnostic and Statistical Manual mood module interview administered by a remote, independent raters, prior to the baseline visit.
- Montgomery-Asberg Depression Scale (MADRS) score of 20 or greater, at Screening and Baseline (MADRS score confirmed to be 20 or greater via remote SAFER interview by an independent rater prior to the baseline visit).
- The following applies to female Subjects: Non-pregnant, non-lactating females of childbearing potential are eligible as long as they agree to use a double barrier method of birth control from Screening until 3 months following discontinuation of IP. Women who are not of childbearing potential (bilateral oophorectomy, bilateral tubal ligation, hysterectomy, or post-menopausal for at least 1 year) will not require such parameters in order to be eligible.
Key exclusion criteria (25 listed)
- Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or other major disease as determined by the Investigator or designee such that participation in the study would place subjects at increased risk for serious adverse events.
- History of cancer or malignancy within the last 5 years. Note: Subjects with basal or squamous cell carcinoma may be permitted into the study on a case by case basis.
- History of seizures; head trauma; or any clinically significant finding on the neurologic examination such that participation in the study would place subjects at increased risk for serious adverse events.
- Previous or current diagnosis of bipolar or schizoaffective disorder or psychotic disorder, or any psychotic symptoms during the current major depressive episode (according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition).
- Subjects who have a concurrent primary psychiatric diagnosis, diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th edition, other than depression.
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 |
|---|---|---|
| 80 Milligrams NSI-189Also: NSI-189 twice per day (BID)Orally Administered | Drug | 80 Milligrams NSI-189, total dose daily |
| PlaceboOrally administered | Drug | 40 Milligrams NSI-189, total dose daily, Placebo Arm |
| 40 Milligrams NSI-189Also: NSI-189 Once a day (QD)Orally Administered | Drug | 40 Milligrams NSI-189, total dose daily |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Up to 12 weeks
6 secondary outcomes
Symptoms of Depression Questionnaire (SDQ)
Time frame: Up to 12 weeks
The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ)
Time frame: Up to 12 weeks
17-item Hamilton Rating Scale for Depression (HAMD17)
Time frame: Up to 12 weeks
Clinical Global Impressions - Severity and Improvement (CGI-S, CGI-I)
Time frame: Up to 12 weeks
Cogstate Brief Battery
Time frame: Up to 12 weeks
CogScreen
Time frame: Up to 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2017.
- Background: PubMed 26643541Fava M, Johe K, Ereshefsky L, Gertsik LG, English BA, Bilello JA, Thurmond LM, Johnstone J, Dickerson BC, Makris N, Hoeppner BB, Flynn M, Mischoulon D, Kinrys G, Freeman MP. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2016 Oct;21(10):1372-80. doi: 10.1038/mp.2015.178. Epub 2015 Dec 8.
- Derived from this study: PubMed 28181668Tajiri N, Quach DM, Kaneko Y, Wu S, Lee D, Lam T, Hayama KL, Hazel TG, Johe K, Wu MC, Borlongan CV. NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats. J Cell Physiol. 2017 Oct;232(10):2731-2740. doi: 10.1002/jcp.25847. Epub 2017 Apr 25.
- Individual participant dataSharing planned: Yes
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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.
Karl Johe, Ph.D. study director
Neuralstem Inc.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 80 Milligrams NSI-189 and 40 Milligrams NSI-189 in people with Major Depressive Disorder, run by Neuralstem Inc. at 13 sites 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 8 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 24 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites 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?
Results are not available in the source record.
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?
Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: Up to 12 weeks). 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 NCT02695472, which also lists 2 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 24 Feb 2017.