DepressionPhase 4NCT00634283
Study of the Effects of an Antidepressant Medication and Placebo on the Brain Functioning of Normal Subjects
A Phase 4 study testing venlafaxine in people with Depression, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This study examines the effects of an antidepressant medication and placebo on the brain functioning of normal subjects. In this study, recordings of brain electrical activity are being used to detect and monitor the response to treatment with venlafaxine IR (Effexor), a drug used for the treatment of depression. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- venlafaxine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Feb 2009
- Phase
- Phase 4
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject age is 18-75 years
- Subject must be in overall good health (i.e., free of any medical condition known to affect brain function).
- Subject must have participated in former study, Physiologic Monitoring of Antidepressant Medication Effects in Normal Controls Subjects (IRB#: 00-11-038-13)
- Subject has had a normal physical exam within one year prior to entry of the study
- Capacity to give Informed Consent
Who cannot join
- Subject has serious medical illness, such as high blood pressure, heart disease, renal impairment, or cirrhosis of the liver.
- Subject meets DSM-IV Axis I criteria for a mood, anxiety, cognitive, or psychiatric disorder; or meets criteria for cluster A or B axis II diagnoses. These disorders will be determined on the basis of a structured assessment with the MINI (Mini International Neuropsychiatric Interview for DSM-IV Axis I Disorders)
- Subject has a history of current or past active suicidal ideation or suicide attempts.
- Subject has received treatment with an antidepressant medication or any medications that could influence brain function since his/her participation in the initial study
- Subject is using any of the following medications which interfere with EEG measures of brain function: Anticholinergics, Barbiturates, Benzodiazepines, Sedating Antihistamines (e.g. diphenhydramine (Benadryl) would be exclusionary, but not loratadine (Claritin))
- Subject has a history of seizures, brain surgery, skull fracture, significant head trauma, or previous abnormal EEG
- Subject is pregnant or planning on becoming pregnancy during course of the study
- Subject is a UCLA student or staff member directly under instruction or employment of any of the investigators
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Los Angeles (UCLA)
Los Angeles, California, 90024
About this study
Official title: Physiologic Monitoring of Antidepressant Medication Effects in Normal Healthy Subjects II
This study examines the effects of an antidepressant medication and placebo on the brain functioning of normal subjects. In this study, recordings of brain electrical activity are being used to detect and monitor the response to treatment with venlafaxine IR (Effexor), a drug used for the treatment of depression. The intent of this study is to test specific hypotheses regarding:
- long-term brain effects of a single course of antidepressant treatment
- pharmaco-conditioning effects underlying antidepressant tolerance/sensitization
- brain functional response to initial versus subsequent antidepressant trials in normal healthy subjects.
Read the detailed description
Major Depressive Disorder (MDD) is a lifelong and recurrent illness, such that many individuals require multiple courses of antidepressant medication treatment. While some patients respond completely to each course of treatment, many do not, and with each unsuccessful antidepressant trial the likelihood that a patient will respond decreases. This raises the possibility that neurophysiologic response in subsequent antidepressant treatment may be influenced by learning processes including sensitization, habituation, and/or classical conditioning. Classical conditioning would entail the association of cues such as pill-taking (conditioned stimuli; CS) with the effects of active medication (unconditioned stimulus; US), such that later presentation of the CS alone would come to elicit a conditioned response (CR). Such effects could be revealed by blinded administration of placebo following a period of treatment with active medication. Habituation effects (tolerance), or sensitization effects (increased response), which require only repeated exposure to a stimulus, might be evidenced after repeated courses of antidepressant treatment. Knowledge of how learning processes impact neurophysiologic response to successive courses of antidepressant treatment would have relevance for clinical populations. Specific hypotheses, however, may be tested in healthy non-clinical samples to avoid potential confounding factors related to severity or chronicity of illness. Learning theories would suggest two hypotheses: (1) neurophysiologic response to placebo will differ between subjects who were previously treated with antidepressant treatment as compared to placebo (classical conditioning hypothesis); and (2) neurophysiologic response to an initial course of antidepressant treatment will differ from response to a repeated course of antidepressant treatment.
- Conditions
- Depression
- Being tested
- venlafaxine
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
venlafaxineDrug
Also called Effexor
venlafaxine IR 150mg
| Study group | Role | What they receive |
|---|---|---|
| antidepressant-experienced | Experimental | Subjects who had previously been exposed to active antidepressant medication (venlafaxine) Receives: Drug: venlafaxine |
| antidepressant-naive | Placebo comparator | Subjects who had previously been exposed to placebo only (and never to active antidepressant medication) Receives: Drug: venlafaxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over Time (4 Weeks).
Cordance values were calculated from conventional 'absolute' and 'relative' qEEG power measures using a three-step procedure. First, EEG power values were computed using a re-attributional electrode montage. Second, the absolute and relative power values were z-transformed to measure deviation from the mean values for each electrode site s in each frequency band f for that recording, yielding Anorm(s,f) and Rnorm(s,f), respectively. Third, these z-scores were summed to yield a cordance "intensity" value, Z, for each electrode in each frequency band where Z(s,f) = Anorm(s,f) + Rnorm(s,f). Analyses for this report focused on changes-from-baseline theta-band (8-12Hz) cordance in the prefrontal region (electrodes Fp1, Fpz, Fp2). Results are defined in terms of positive and negative change where a positive change represents an increased physiologic and behavioral response to the drug (sensitization) and a negative change represents an increased tolerance to the drug (habituation).
Measured: Average over 4 weeks
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over 1 Week Placebo lead-in.
Cordance values were calculated from conventional 'absolute' and 'relative' qEEG power measures using a three-step procedure. First, EEG power values were computed using a re-attributional electrode montage. Second, the absolute and relative power values were z-transformed to measure deviation from the mean values for each electrode site s in each frequency band f for that recording, yielding Anorm(s,f) and Rnorm(s,f), respectively. Third, these z-scores were summed to yield a cordance "intensity" value, Z, for each electrode in each frequency band where Z(s,f) = Anorm(s,f) + Rnorm(s,f). Analyses for this report focused on changes-from-baseline theta-band (8-12Hz) cordance in the prefrontal region (electrodes Fp1, Fpz, Fp2). Results are defined in terms of positive and negative change where a positive change represents an increased physiologic and behavioral response to the drug (sensitization) and a negative change represents an increased tolerance to the drug (habituation).
Measured: 1-week placebo lead-in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionFeb 2009
- Study completionFeb 2009
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 (1)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects are assigned to one of two groups (antidepressant-experienced and antidepressant-naive) and receive parallel treatment (1 week of placebo followed by 4 weeks of venlafaxine) for the duration of the study. Subjects and assessors were blinded to treatment condition.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew F. Leuchter, University of California, Los Angeles
- Investigators
- Andrew Leuchter, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00634283
- Sponsor's protocol ID
- 07-10-051
- Status last verified
- Feb 2020
- First submitted
- 6 Mar 2008
- Last updated
- 9 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Hunter AM, Cook IA, Abrams M, Leuchter AF. Neurophysiologic effects of repeated exposure to antidepressant medication: are brain functional changes during antidepressant administration influenced by learning processes? Med Hypotheses. 2013 Dec;81(6):1004-11. doi: 10.1016/j.mehy.2013.09.016. Epub 2013 Sep 17.
PubMed 24112999
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiologic Monitoring of Antidepressant Medication Effects in Normal Healthy Subjects II
- ClinicalTrials.gov ID
- NCT00634283
- Acronym / sponsor ID
- 07-10-051
- Conditions
- Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 18 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study examines the effects of an antidepressant medication and placebo on the brain functioning of normal subjects. In this study, recordings of brain electrical activity are being used to detect and monitor the response to treatment with venlafaxine IR (Effexor), a drug used for the treatment of depression. The intent of this study is to test specific hypotheses regarding:
- long-term brain effects of a single course of antidepressant treatment
- pharmaco-conditioning effects underlying antidepressant tolerance/sensitization
- brain functional response to initial versus subsequent antidepressant trials in normal healthy subjects.
Detailed description
Major Depressive Disorder (MDD) is a lifelong and recurrent illness, such that many individuals require multiple courses of antidepressant medication treatment. While some patients respond completely to each course of treatment, many do not, and with each unsuccessful antidepressant trial the likelihood that a patient will respond decreases. This raises the possibility that neurophysiologic response in subsequent antidepressant treatment may be influenced by learning processes including sensitization, habituation, and/or classical conditioning. Classical conditioning would entail the association of cues such as pill-taking (conditioned stimuli; CS) with the effects of active medication (unconditioned stimulus; US), such that later presentation of the CS alone would come to elicit a conditioned response (CR). Such effects could be revealed by blinded administration of placebo following a period of treatment with active medication. Habituation effects (tolerance), or sensitization effects (increased response), which require only repeated exposure to a stimulus, might be evidenced after repeated courses of antidepressant treatment. Knowledge of how learning processes impact neurophysiologic response to successive courses of antidepressant treatment would have relevance for clinical populations. Specific hypotheses, however, may be tested in healthy non-clinical samples to avoid potential confounding factors related to severity or chronicity of illness. Learning theories would suggest two hypotheses: (1) neurophysiologic response to placebo will differ between subjects who were previously treated with antidepressant treatment as compared to placebo (classical conditioning hypothesis); and (2) neurophysiologic response to an initial course of antidepressant treatment will differ from response to a repeated course of antidepressant treatment.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects are assigned to one of two groups (antidepressant-experienced and antidepressant-naive) and receive parallel treatment (1 week of placebo followed by 4 weeks of venlafaxine) for the duration of the study. Subjects and assessors were blinded to treatment condition.
| Arm | Type | Receives |
|---|---|---|
| antidepressant-experienced | Experimental | Drug: venlafaxineSubjects who had previously been exposed to active antidepressant medication (venlafaxine) |
| antidepressant-naive | Placebo comparator | Drug: venlafaxineSubjects who had previously been exposed to placebo only (and never to active antidepressant medication) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject age is 18-75 years
- Subject must be in overall good health (i.e., free of any medical condition known to affect brain function).
- Subject must have participated in former study, Physiologic Monitoring of Antidepressant Medication Effects in Normal Controls Subjects (IRB#: 00-11-038-13)
- Subject has had a normal physical exam within one year prior to entry of the study
- Capacity to give Informed Consent
Key exclusion criteria (8 listed)
- Subject has serious medical illness, such as high blood pressure, heart disease, renal impairment, or cirrhosis of the liver.
- Subject meets DSM-IV Axis I criteria for a mood, anxiety, cognitive, or psychiatric disorder; or meets criteria for cluster A or B axis II diagnoses. These disorders will be determined on the basis of a structured assessment with the MINI (Mini International Neuropsychiatric Interview for DSM-IV Axis I Disorders)
- Subject has a history of current or past active suicidal ideation or suicide attempts.
- Subject has received treatment with an antidepressant medication or any medications that could influence brain function since his/her participation in the initial study
- Subject is using any of the following medications which interfere with EEG measures of brain function: Anticholinergics, Barbiturates, Benzodiazepines, Sedating Antihistamines (e.g. diphenhydramine (Benadryl) would be exclusionary, but not loratadine (Claritin))
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 |
|---|---|---|
| venlafaxineAlso: Effexorvenlafaxine IR 150mg | Drug | antidepressant-experienced, antidepressant-naive |
Primary outcome
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over Time (4 Weeks).
Time frame: Average over 4 weeks
Cordance values were calculated from conventional 'absolute' and 'relative' qEEG power measures using a three-step procedure. First, EEG power values were computed using a re-attributional electrode montage. Second, the absolute and relative power values were z-transformed to measure deviation from the mean values for each electrode site s in each frequency band f for that recording, yielding Anorm(s,f) and Rnorm(s,f), respectively. Third, these z-scores were summed to yield a cordance "intensity" value, Z, for each electrode in each frequency band where Z(s,f) = Anorm(s,f) + Rnorm(s,f). Analyses for this report focused on changes-from-baseline theta-band (8-12Hz) cordance in the prefrontal region (electrodes Fp1, Fpz, Fp2). Results are defined in terms of positive and negative change where a positive change represents an increased physiologic and behavioral response to the drug (sensitization) and a negative change represents an increased tolerance to the drug (habituation).
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over 1 Week Placebo lead-in.
Time frame: 1-week placebo lead-in
Cordance values were calculated from conventional 'absolute' and 'relative' qEEG power measures using a three-step procedure. First, EEG power values were computed using a re-attributional electrode montage. Second, the absolute and relative power values were z-transformed to measure deviation from the mean values for each electrode site s in each frequency band f for that recording, yielding Anorm(s,f) and Rnorm(s,f), respectively. Third, these z-scores were summed to yield a cordance "intensity" value, Z, for each electrode in each frequency band where Z(s,f) = Anorm(s,f) + Rnorm(s,f). Analyses for this report focused on changes-from-baseline theta-band (8-12Hz) cordance in the prefrontal region (electrodes Fp1, Fpz, Fp2). Results are defined in terms of positive and negative change where a positive change represents an increased physiologic and behavioral response to the drug (sensitization) and a negative change represents an increased tolerance to the drug (habituation).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24112999Hunter AM, Cook IA, Abrams M, Leuchter AF. Neurophysiologic effects of repeated exposure to antidepressant medication: are brain functional changes during antidepressant administration influenced by learning processes? Med Hypotheses. 2013 Dec;81(6):1004-11. doi: 10.1016/j.mehy.2013.09.016. Epub 2013 Sep 17.
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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.
Andrew Leuchter, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing venlafaxine in people with Depression, run by University of California, Los Angeles 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 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 9 Mar 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Feb 2020). 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?
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over Time (4 Weeks). (time frame: Average over 4 weeks). The study lists 2 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 NCT00634283, which also lists 1 linked publication.
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 9 Mar 2020.