Major Depressive Disorder (MDD)Phase 1NCT01701258

An Investigation of Early Life Stress and Depression

A Phase 1 study testing Amisulpride in people with Major Depressive Disorder (MDD) and History of Childhood Sexual Abuse (CSA), run by Mclean Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to investigate brain pathways within adult females (with a history of CSA that occurred between the ages of 5-14) with and without a current diagnosis of major depressive disorder (MDD). Read more about this study

Who is it for?: Ages 20 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for: Major Depressive Disorder (MDD), History of Childhood Sexual Abuse (CSA)
What is being tested?: Amisulpride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 153 participants
Where: 2 sitesUnited States
Study dates: Aug 2013to May 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 20 to 45 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of SCID);
Non-traumatized, healthy controls (controls):
No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
Absence of any medical, neurological, and psychiatric illness (including alcohol/substance abuse)

Who cannot join

Participants with suicidal ideation where study participation is deemed unsafe by the study clinician;
Pregnant women or women of childbearing potential who are not compliant with the requirements of a urine and blood pregnancy test.
Failure to meet MRI or PET safety requirements.
Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine (hypothyroidism), neurologic or hematologic disease;
Past/current DSM diagnosis of: OCD, ADHD, schizophrenia, schizoaffective disorder, delusional disorder, bipolar disorder, mood congruent/incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion);
Simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD and only in the CSA/MDD and MDD groups (which will be matched for comorbidities);
History of seizure disorder; renal insufficiency; history of adverse reactions to amisulpride;
History of cocaine, stimulant, and other DA drug use [e.g., (meth)amphetamine), methylphenidate].

Trial locations and contacts

2 sites in 1 country.

United States2 sites

McLean Hospital
Belmont, Massachusetts, 02478
Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Early Life Stress and Depression: Molecular and Functional Imaging Approaches

Hypotheses:

The CSA/MDD participants will be characterized by (1) reduced reward responsiveness and prefrontal cortex activity, but increased cortisol levels, (2) reduced dopamine activity, and (3) reduced dopamine transporter binding. The over-arching purpose of the study is to (1) identify individuals at risk for psychopathology and maladaptive behavior, (2) prevent re-victimization, and (3) develop more targeted therapeutic interventions.

Read the detailed description

This study will include four sessions:

Session 1 (SCID Session) The first session takes place at the Center for Depression, Anxiety, and Stress Research (CDASR) or Neuroimaging Center (both at McLean Hospital) and involves consenting, a clinical evaluation, a series of questionnaires, and a medical assessment.

Session 2 or 3 (fMRI Session) The third session takes place at the Neuroimaging Center. Using a double-blind design, participants will be administered either amisulpride (50 mg) or placebo. Participants will complete the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging (fMRI) and the Probabilistic Stimulus Selection Task (PSST) afterwards.

Session 2 or 3 (PET Session) This session takes place at Massachusetts General Hospital. 9 mCi of [11C] altropane will be injected by a trained nuclear medicine technician and positron emission tomography (PET) scanning will begin. Prior to the PET scan, a blood serum pregnancy test will be administered for females.

Session 4 (ERP Session) The fourth session takes place at the CDASR and involves an electroencephalography (EEG) recording, the Probabilistic Reward Task (PRT), and collecting saliva samples to assess cortisol levels.

Conditions: Major Depressive Disorder (MDD), History of Childhood Sexual Abuse (CSA)
Being tested: Amisulpride, Placebo
Keywords: Depression, Childhood Sexual Abuse, Dopamine, MRI, PET, ERP, Stress, Reward, Childhood trauma, Amisulpride
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.

AmisulprideDrug
Also called Solian
single low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only
PlaceboDrug
single-dose placebo capsule during the fMRI session only

Study groups in NCT01701258
Study group	Role	What they receive
CSA/MDD-amisulpride	Active comparator	Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. Receives: Drug: Amisulpride
CSA/MDD-placebo	Placebo comparator	Subjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a placebo during the fMRI session. Receives: Drug: Placebo
CSA/RES-amisulpride	Active comparator	Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. Receives: Drug: Amisulpride
CSA/RES-placebo	Placebo comparator	Subjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a placebo during the fMRI session. Receives: Drug: Placebo
MDD-amisulpride	Active comparator	Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. Receives: Drug: Amisulpride
MDD-placebo	Placebo comparator	Subjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a placebo during the fMRI session. Receives: Drug: Placebo
Control-amisulpride	Active comparator	Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session. Receives: Drug: Amisulpride
Control-placebo	Placebo comparator	Subjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a placebo during the fMRI session. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Dopamine Active Transporter Binding Potential
Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine active transporter (DAT) binding potential.
Our outcome measure is Nondisplacable Binding Potential (BPND). BPND refers to the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue.
*Higher BPND scores indicate greater binding potential
Measured: 1 hour PET scan (Session 3)
The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress
The participant's performance on the Probabilistic Reward Task (PRT) was assessed both before and after an acute stressor. The PRT is a behavioral task that measures an individual's ability to learn from rewarding stimuli and incorporate this learning into their response style (response bias). The acute stressor was the Maastricht Acute Stress Test (MAST). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli. Response bias scores range between -1 and +1. Higher response bias scores indicate a stronger response bias toward high reward stimuli. A negative response bias indicates a stronger bias toward low reward stimuli.
Measured: 3 hour EEG Session (Session 4)
The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress
EEG was recorded during the probabilistic reward task (the PRT task). Participants completed the Probabilistic Reward Task (PRT) twice throughout the experiment, once before stress and once after stress. The stressor was the Maastricht Acute Stress Test (MAST). This statistic shows the effect that childhood sexual abuse (CSA) and diagnosis had on a reward-related positivity EEG component recorded during the PRT, before and after stress.
- Higher reward positivity amplitudes indicate a stronger neural response to reward and lower amplitudes indicate a lower neural response to rewards.
Measured: 3 hour EEG Session (Session 4)
Cortisol Output in Response to a Stress Manipulation
This statistic shows the impact of the stress manipulation on the participant's salivary cortisol output. Saliva samples were collected at 5 distinct time points throughout the study session. The first saliva sample (Cort 1) was collected when the participant began the eeg session. The second (Cort 2)was taken at the end of the acute stressor. The third (Cort 3) was taken approximately fifteen minutes after the second. The fourth (Cort 4) was taken approximately ten minutes after the third. The fifth (Cort 5) was taken approximately 40 minutes after the fourth.
Measured: 3 hour EEG Session (Session 4)
Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues
This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward cues during the monetary incentive delay task (MID).
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.
Measured: 3 hour Drug & fMRI Session (Session 2)
Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback
This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward feedback during the monetary incentive delay task (MID).
Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.
Measured: 3 hour Session 2 (fMRI session)
The Effect of Diagnosis on Cortisol Reactivity
This is a measure of area under the curve in relation to ground, a measure of total cortisol output, in response to acute stress. The acute stressor was the Maastricht Acute Stress Test (MAST). The area under the curve includes all 5 cortisol measures, with one measure before the stressor and the other four measures collected after the stressor. Given that the cortisol data were positively skewed, the cortisol measures were normalized via a log transformation prior to calculating the area under the curve.
Area under the curve with respect to ground (AUCG) is calculated AUC_g=(((cort2_log + cort1_log) * cort_t1_time) / 2)+(((cort3_log+cort2_log)*cort_t2_time)/2)+(((cort4_log+cort3_log)*cort_t3_time)/2)+(((cort5_log+cort4_log)*cort_t4_time)/2). Cort_logs are the log transformed cortisol output data (ng/ml) and the cort_times are the time spans in between each cortisol assessment.
Measured: 3 hour EEG Session (Session 4)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2013May 2017

First posted5 Oct 2012 (estimated)
Study startAug 2013
Primary completionMay 2017
Study completionMay 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Major Depressive Disorder (MDD)Studies 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 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Model description: There were four groups of subjects: those with a history of child sexual abuse that are currently experiencing a major depressive episode, those with a history of child sexual abuse without a current or past diagnosis of major depressive disorder, those without a history of child sexual abuse that are currently experiencing a major depressive episode, and those with without a history of child sexual abuse and without a current or past diagnosis of major depressive disorder. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo for the fMRI session (session 2 or 3).
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 153 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01701258
Sponsor's protocol ID: 2012P002593
Other IDs: 5R01MH095809
Status last verified: May 2025
First submitted: 2 Oct 2012
Last updated: 7 May 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Kaiser RH, Clegg R, Goer F, Pechtel P, Beltzer M, Vitaliano G, Olson DP, Teicher MH, Pizzagalli DA. Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response. Psychol Med. 2018 May;48(7):1157-1166. doi: 10.1017/S0033291717002628. Epub 2017 Sep 25.
PubMed 28942738
Liu Y, Admon R, Mellem MS, Belleau EL, Kaiser RH, Clegg R, Beltzer M, Goer F, Vitaliano G, Ahammad P, Pizzagalli DA. Machine Learning Identifies Large-Scale Reward-Related Activity Modulated by Dopaminergic Enhancement in Major Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):163-172. doi: 10.1016/j.bpsc.2019.10.002. Epub 2019 Oct 22.
PubMed 31784354

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Early Life Stress and Depression: Molecular and Functional Imaging Approaches
ClinicalTrials.gov ID: NCT01701258
Acronym / sponsor ID: 2012P002593
Conditions: Major Depressive Disorder (MDD), History of Childhood Sexual Abuse (CSA)
Keywords: Depression, Childhood Sexual Abuse, Dopamine, MRI, PET, ERP, Stress, Reward
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 153 participants (actual)
Lead sponsor: Mclean HospitalUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH), Massachusetts General Hospital
Study start: Aug 2013 (actual)
Primary completion: May 2017 (actual)
Study completion: May 2017 (actual)
First posted: 5 Oct 2012 (estimated)
Results: Posted 18 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Hypotheses:

Detailed description

This study will include four sessions:

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 8
Model description: There were four groups of subjects: those with a history of child sexual abuse that are currently experiencing a major depressive episode, those with a history of child sexual abuse without a current or past diagnosis of major depressive disorder, those without a history of child sexual abuse that are currently experiencing a major depressive episode, and those with without a history of child sexual abuse and without a current or past diagnosis of major depressive disorder. Within each group, half of the subjects were assigned to receive the study drug (amisulpride) and half to receive a placebo for the fMRI session (session 2 or 3).

Arm	Type	Receives
CSA/MDD-amisulpride	Active comparator	Drug: AmisulprideSubjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
CSA/MDD-placebo	Placebo comparator	Drug: PlaceboSubjects experiencing a current episode of major depression (MDD) with a history of child sexual abuse (CSA) are randomized to receive a placebo during the fMRI session.
CSA/RES-amisulpride	Active comparator	Drug: AmisulprideSubjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
CSA/RES-placebo	Placebo comparator	Drug: PlaceboSubjects with a history of child sexual abuse (CSA) without a current or past diagnosis of major depressive disorder (RES) are randomized to receive a placebo during the fMRI session.
MDD-amisulpride	Active comparator	Drug: AmisulprideSubjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
MDD-placebo	Placebo comparator	Drug: PlaceboSubjects without a history of child sexual abuse that are currently experiencing a major depressive episode are randomized to receive a placebo during the fMRI session.
Control-amisulpride	Active comparator	Drug: AmisulprideSubjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a single low-dose pharmacological challenge, 50mg amisulpride tablet during the fMRI session.
Control-placebo	Placebo comparator	Drug: PlaceboSubjects without a history of child sexual abuse and without a current or past diagnosis of major depressive episode are randomized to receive a placebo during the fMRI session.

Who may qualify

Ages: 20 to 45 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
Current DSM-IV diagnostic criteria for MDD (as diagnosed with the use of SCID);
No incidents of sexual, verbal, or physical abuse (ascertained using the Traumatic Antecedents Questionnaire);
Absence of any medical, neurological, and psychiatric illness (including alcohol/substance abuse)

Key exclusion criteria (8 listed)

Participants with suicidal ideation where study participation is deemed unsafe by the study clinician;
Pregnant women or women of childbearing potential who are not compliant with the requirements of a urine and blood pregnancy test.
Failure to meet MRI or PET safety requirements.
Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine (hypothyroidism), neurologic or hematologic disease;
Past/current DSM diagnosis of: OCD, ADHD, schizophrenia, schizoaffective disorder, delusional disorder, bipolar disorder, mood congruent/incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion);

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
AmisulprideAlso: Soliansingle low-dose pharmacological challenge, 50 mg amisulpride during the fMRI session only	Drug	CSA/MDD-amisulpride, CSA/RES-amisulpride, Control-amisulpride, MDD-amisulpride
Placebosingle-dose placebo capsule during the fMRI session only	Drug	CSA/MDD-placebo, CSA/RES-placebo, Control-placebo, MDD-placebo

Primary outcome

Dopamine Active Transporter Binding Potential
Time frame: 1 hour PET scan (Session 3)
Utilizing 11C-altropane during positron emission tomography (PET) scanning allows us to measure dopamine active transporter (DAT) binding potential. Our outcome measure is Nondisplacable Binding Potential (BPND). BPND refers to the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue. *Higher BPND scores indicate greater binding potential
The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress
Time frame: 3 hour EEG Session (Session 4)
The participant's performance on the Probabilistic Reward Task (PRT) was assessed both before and after an acute stressor. The PRT is a behavioral task that measures an individual's ability to learn from rewarding stimuli and incorporate this learning into their response style (response bias). The acute stressor was the Maastricht Acute Stress Test (MAST). The score obtained is a ratio of the number of times participants correctly choose the high reward stimuli versus the low rewarding stimuli. Response bias scores range between -1 and +1. Higher response bias scores indicate a stronger response bias toward high reward stimuli. A negative response bias indicates a stronger bias toward low reward stimuli.
The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress
Time frame: 3 hour EEG Session (Session 4)
EEG was recorded during the probabilistic reward task (the PRT task). Participants completed the Probabilistic Reward Task (PRT) twice throughout the experiment, once before stress and once after stress. The stressor was the Maastricht Acute Stress Test (MAST). This statistic shows the effect that childhood sexual abuse (CSA) and diagnosis had on a reward-related positivity EEG component recorded during the PRT, before and after stress. * Higher reward positivity amplitudes indicate a stronger neural response to reward and lower amplitudes indicate a lower neural response to rewards.
Cortisol Output in Response to a Stress Manipulation
Time frame: 3 hour EEG Session (Session 4)
This statistic shows the impact of the stress manipulation on the participant's salivary cortisol output. Saliva samples were collected at 5 distinct time points throughout the study session. The first saliva sample (Cort 1) was collected when the participant began the eeg session. The second (Cort 2)was taken at the end of the acute stressor. The third (Cort 3) was taken approximately fifteen minutes after the second. The fourth (Cort 4) was taken approximately ten minutes after the third. The fifth (Cort 5) was taken approximately 40 minutes after the fourth.
Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Cues
Time frame: 3 hour Drug & fMRI Session (Session 2)
This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward cues during the monetary incentive delay task (MID). Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.
Effects on Major Depressive Disorder and Childhood Sexual Abuse History on Striatal Activity in Response to Neutral and Reward Feedback
Time frame: 3 hour Session 2 (fMRI session)
This statistic shows the influence of major depressive disorder and childhood sexual abuse history on the strength of striatal activation (caudate, putamen, accumbens) in response to neutral and reward feedback during the monetary incentive delay task (MID). Striatal activation is measured using a statistic called a beta weight. A beta weight is a standardized regression coefficient. Higher beta weights mean greater striatal activation and lower beta weights mean less striatal activation. A negative beta weight would indicate a deactivation.
The Effect of Diagnosis on Cortisol Reactivity
Time frame: 3 hour EEG Session (Session 4)
This is a measure of area under the curve in relation to ground, a measure of total cortisol output, in response to acute stress. The acute stressor was the Maastricht Acute Stress Test (MAST). The area under the curve includes all 5 cortisol measures, with one measure before the stressor and the other four measures collected after the stressor. Given that the cortisol data were positively skewed, the cortisol measures were normalized via a log transformation prior to calculating the area under the curve. Area under the curve with respect to ground (AUCG) is calculated AUC_g=(((cort2_log + cort1_log) * cort_t1_time) / 2)+(((cort3_log+cort2_log)*cort_t2_time)/2)+(((cort4_log+cort3_log)*cort_t3_time)/2)+(((cort5_log+cort4_log)*cort_t4_time)/2). Cort_logs are the log transformed cortisol output data (ng/ml) and the cort_times are the time spans in between each cortisol assessment.

Results and safety

Results posted to the registry on 18 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Participants	153	70
Control Group	0	0
Control-amisulpride (fMRI Session)	0	0
Control-placebo (fMRI Session)	0	0
MDD Group	0	0
MDD-amisulpride (fMRI Session)	0	0
MDD-placebo (fMRI Session)	0	0
CSA/RES	0	0
CSA/RES-amisulpride (fMRI Session)	0	0
CSA/RES-placebo (fMRI Session)	0	0
CSA/MDD Group	0	0
CSA/MDD-amisulpride (fMRI Session)	0	0
CSA/MDD-placebo (fMRI Session)	0	0

Primary outcome: Dopamine Active Transporter Binding Potential

Time frame: 1 hour PET scan (Session 3). Mean (Standard Error). Unit: Ratio

Measure	Control Group n = 20	MDD Group n = 16	CSA/RES Group n = 19	CSA/MDD Group n = 18
Caudate	3.191 (0.124)	3.161 (0.139)	3.175 (0.130)	3.216 (0.136)
Putamen	3.361 (0.120)	3.359 (0.134)	3.241 (0.125)	3.318 (0.131)
Accumbens	2.159 (0.109)	2.103 (0.122)	2.103 (0.122)	2.149 (0.119)

Primary outcome: The Effects of CSA and Diagnosis on PRT Performance Under Acute Stress

Time frame: 3 hour EEG Session (Session 4). Mean (Standard Deviation). Unit: Ratio (Response Bias Score)

Measure	Control Group n = 19	MDD Group n = 14	CSA/RES Group n = 16	CSA/MDD Group n = 17
PRT Block1: Before MAST	0.028 (0.035)	0.117 (0.045)	0.092 (0.043)	0.167 (0.070)
PRT Block2: Before MAST	0.124 (0.046)	0.155 (0.048)	0.130 (0.082)	0.168 (0.102)
PRT Block1: After MAST	0.128 (0.026)	0.078 (0.055)	0.079 (0.042)	0.048 (0.042)
PRT Block2: After MAST	0.245 (0.041)	0.128 (0.035)	0.143 (0.052)	0.127 (0.050)

Primary outcome: The Effect of Major Depressive Disorder and Childhood Abuse History on a Reward-related EEG Component (Reward Positivity Component) While Under Stress

Time frame: 3 hour EEG Session (Session 4). Mean (Standard Error). Unit: amplitude (microvolts)

Measure	Control Group n = 19	MDD Group n = 14	CSA/RES Group n = 16	CSA/MDD Group n = 17
Pre MAST	2.71 (0.86)	4.75 (1.15)	2.16 (0.92)	4.15 (0.96)
Post MAST	2.06 (0.91)	4.99 (1.22)	2.30 (0.98)	3.90 (1.01)

Primary outcome: Cortisol Output in Response to a Stress Manipulation

Time frame: 3 hour EEG Session (Session 4). Mean (Standard Error). Unit: ng/ml

Measure	Control Group n = 19	MDD Group n = 14	CSA/RES Group n = 16	CSA/MDD Group n = 17
Cort1	9.80 (1.27)	12.53 (2.11)	10.15 (2.27)	14.19 (1.51)
Cort2	9.11 (2.44)	12.28 (1.70)	9.51 (1.89)	8.63 (0.95)
Cort3	15.55 (4.91)	15.23 (1.65)	10.75 (2.19)	14.31 (2.15)
Cort4	12.89 (4.07)	16.30 (3.24)	8.99 (1.75)	14.22 (2.74)
Cort5	7.07 (1.80)	10.34 (1.15)	7.41 (1.36)	11.01 (2.15)

Adverse events

Time frame: 3 years, 10 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Participants	0 of 153 (0%)	0 of 153 (0%)	0 of 153
All Baseline Participants	0 of 96 (0%)	0 of 96 (0%)	0 of 96
Control Group	0 of 26 (0%)	0 of 26 (0%)	0 of 26
Control-amisulpride (fMRI Session)	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Control-placebo (fMRI Session)	0 of 11 (0%)	0 of 11 (0%)	0 of 11
MDD Group	0 of 17 (0%)	0 of 17 (0%)	0 of 17
MDD-amisulpride (fMRI Session)	0 of 9 (0%)	0 of 9 (0%)	0 of 9
MDD-placebo (fMRI Session)	0 of 8 (0%)	0 of 8 (0%)	0 of 8
CSA/RES	0 of 24 (0%)	0 of 24 (0%)	0 of 24
CSA/RES-amisulpride (fMRI Session)	0 of 6 (0%)	0 of 6 (0%)	0 of 6
CSA/RES-placebo (fMRI Session)	0 of 6 (0%)	0 of 6 (0%)	0 of 6
CSA/MDD Group	0 of 29 (0%)	0 of 29 (0%)	0 of 29
CSA/MDD-amisulpride (fMRI Session)	0 of 10 (0%)	0 of 10 (0%)	0 of 10
CSA/MDD-placebo (fMRI Session)	0 of 7 (0%)	0 of 7 (0%)	0 of 7

Limitations and caveats (from the sponsor): The choice of a 50-mg dose of amisulpride was based on animal work showing low doses potentiate striatal dopamine release, have strong hedonic effects, and increase the incentive value of environmental cues. Higher doses may have different results.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28942738Kaiser RH, Clegg R, Goer F, Pechtel P, Beltzer M, Vitaliano G, Olson DP, Teicher MH, Pizzagalli DA. Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response. Psychol Med. 2018 May;48(7):1157-1166. doi: 10.1017/S0033291717002628. Epub 2017 Sep 25.
Derived from this study: PubMed 31784354Liu Y, Admon R, Mellem MS, Belleau EL, Kaiser RH, Clegg R, Beltzer M, Goer F, Vitaliano G, Ahammad P, Pizzagalli DA. Machine Learning Identifies Large-Scale Reward-Related Activity Modulated by Dopaminergic Enhancement in Major Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb;5(2):163-172. doi: 10.1016/j.bpsc.2019.10.002. Epub 2019 Oct 22.
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.

Diego Pizzagalli, PhD principal investigator

Mclean Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Amisulpride in people with Major Depressive Disorder (MDD) and History of Childhood Sexual Abuse (CSA), run by Mclean Hospital at 2 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 5 inclusion and 8 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 7 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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?

Yes. Results are posted in the registry (first posted 18 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dopamine Active Transporter Binding Potential (time frame: 1 hour PET scan (Session 3)). The study lists 7 primary outcomes in all. 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 NCT01701258, 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 7 May 2025.