Mood DisordersPhase 2NCT00055575
Cholinergic Modulation of Condition and Emotion in Mood Disorders: Functional Neuroimaging Studies
A Phase 2 study testing Scopolamine Nasal Spray in people with Mood Disorders and Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study looks at the role of a specific brain chemical system in the mood and attention symptoms seen in major depression and bipolar disorders using functional brain imaging. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Mood Disorders, Healthy, Unipolar Depression
- What is being tested?
- Scopolamine Nasal Spray
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 197 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2003to 2 Feb 2015
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients with Major Depressive Disorder (MDD):
- Age 18-55
- Current diagnosis of MDD, as defined by DSM-IV criteria for recurrent MDD
- Current depressive episode
- Current IDS score in the moderately-to-severely depressed range
- Right handed
Show all 18Show fewer
- Able to provide informed consent
- Patients with Bipolar Disorder (BD):
- Age 18-55
- Current diagnosis of bipolar disorder, as defined by DSM-IV
- Current depressive episode
- Current IDS score in the moderately-to-severely depressed range
- Right handed
- Able to provide informed consent
- Healthy Controls:
- Age 18-55
- Able to provide informed consent
- Medically healthy
Who cannot join
- Patients MDD \& BD:
- Serious suicidal ideation or behavior (with a current plan or intent), or current delusions or hallucinations
- Medical or neurological illnesses likely to affect physiology or anatomy
- History of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria)
- Current or past history of other axis I disorders that preceded the onset of MDD or BD
- Current pregnancy (documented by pregnancy testing within 24 hours prior to pilot studies and 24 hours prior to scanning)
Show all 30Show fewer
- Current breast feeding
- General MRI exclusion criteria (including the presence of pacemakers, cochlear implants, surgical clips or metal fragments in their eyes or body parts)
- Vision and/or hearing problems severe enough to interfere with testing
- Electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction
- Current blood pressure of >140 mm Hg or < 90 mm Hg systolic, or > 90 mm Hg diastolic (due to the potential cardiovascular effects of scopolamine and physostigmine)
- Clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, advanced arteriosclerosis, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncrasy to anticholinergic agents, glaucoma, renal or hepatic impairment
- Clinical history of glaucoma or narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine)
- Age of onset greater than 45 years (to reduce the biological heterogeneity encompassed by the MDD and BD criteria, since subjects with a late age-at onset for depression have a far greater likelihood of having MRI correlates of cerebrovascular disease than age-matched, healthy controls or age-matched, early-onset depressives)
- Exposure within two weeks to medications likely to effect cerebral blood flow and metabolism or likely to interact with anti-cholinergic medications (e.g. narcotics or anti-cholinergic agents)- as verified by history and urine drug screen
- HIV positive status
- Weight over 275 pounds
- Healthy Controls:
- Medical or neurological illness
- Current pregnancy (documented by pregnancy testing within 24 hours prior to pilot studies and 24 hours prior to scanning)
- Current breast feeding
- General MRI exclusion criteria (including the presence of pacemakers, cochlear implants, surgical clips or metal fragments in their eyes or body parts)
- Vision and/or hearing problems severe enough to interfere with testing
- Electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction
- Current blood pressure of >140 mm Hg or < 90 mm Hg systolic, or > 90 mm Hg diastolic (due to the potential cardiovascular effects of scopolamine and physostigmine)
- Clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, advanced arteriosclerosis, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncrasy to anticholinergic agents, glaucoma, renal or hepatic impairment
- Clinical history of glaucoma or narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine)
- HIV positive status
- Weight over 275 pounds
- For BD patients being recruited for the scopolamine efficacy trial, they may forgo imaging and thus will not be excluded for imaging related exclusion criteria (including general MRI exclusion criteria and vision and/or hearing problems).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Cholinergic Modulation of Cognition and Emotion in Mood Disorders: Functional Neuroimaging Studies
This study looks at the role of a specific brain chemical system in the mood and attention symptoms seen in major depression and bipolar disorders using functional brain imaging.
Read the detailed description
- Objective The goal of this research project is to evaluate the role of the cholinergic system in behavioral and cognitive symptoms observed in mood disorders in humans, using functional brain neuroimaging techniques. Specific aspects of behavior and cognition are impaired in mood disorders, including selective attention, set-shifting and memory; and there is also evidence that depressed subjects exhibit a mood congruent processing bias whereby they more readily process negatively toned information as compared to positively toned information. This cognitive pattern lends itself to evaluation with functional brain imaging, both in terms of identifying the anatomical correlates of the specific behavioral and cognitive deficits as well as characterizing the effects of pharmacological manipulation. Attention and memory functions are closely tied to the cholinergic neurotransmitter system. The cholinergic system is one of the neurotransmitter systems implicated in the pathophysiology of mood disorders. Evidence suggests that during major depressive episodes, the cholinergic system is hypersensitive to acetylcholine. Agents that enhance muscarinic cholinergic receptor function increase depressive symptoms in depressed subjects, and can produce symptoms of depression in healthy subjects. The preclinical literature more specifically implicates the muscarinic receptors and indicates that the use of muscarinic antagonists, in the context of animal models of depression, results in improvement in the behavioral analogs of depression.
- Study Population The accrual ceiling for this protocol is 388 participants. 143 currently depressed patients with major depressive disorder, 100 currently depressed patients with bipolar disorder, and 145 healthy controls will participate in this study.
- Design The antimuscarinic agent, scopolamine, will be administered in a double-blind, placebo controlled manner across all studies. Clinical ratings, cognitive tasks and neuroimaging will be conducted at various timepoints to evaluate the clinical effects of scopolamine on depression, to assess the acute mood response to scopolamine; and to study the neurobiological correlates of the clinical and behavioral drug effects.
- Outcome Measures
The proposed inpatient or outpatient project investigates the role of cholinergic neurotransmission in the behavioral and cognitive symptoms observed in the depressed phase of both major depressive disorder (MDD) and bipolar disorder (BD). The studies proposed here will identify anatomical correlates of the mood congruent processing bias, working memory, attention and set-shifting deficits observed in depressed subjects. Further, these studies will evaluate the effects of the cholinergic antagonist, scopolamine, both on the performance deficits and on neural activity in brain regions recruited as subjects perform these tasks.
Dose escalation studies will be conducted to determine if higher doses of scopolamine will increase the antidepressant response rate in patients with major depressive disorder. Based on earlier work showing the predictive value in baseline neuroimaging data to predict treatment outcome, we will stratify participants at baseline into groups based on expected response to scopolamine treatment.
This approach is expected to reveal how neuromodulators influence processing in brain structures recruited to perform these tasks, both in healthy subjects and in major depressive disorders. The combined use of functional brain imaging and pharmacological manipulation to evaluate the role of neurotransmitter dysfunction in depression may direct us to potential therapeutic approaches.
- Conditions
- Mood Disorders, Healthy, Unipolar Depression, Bipolar Depression
- Being tested
- Scopolamine Nasal Spray
- Keywords
- Scopolamine, Depression, fMRI, Cognition, Emotion, Brain, Bipolar Disorder, Major Depressive Disorder, MDD, Healthy Volunteer, HV
- Medical subject headings
- Mood Disorders, Depressive Disorder, Bipolar Disorder, Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Scopolamine Nasal SprayDrug
| Study group | Role | What they receive |
|---|---|---|
| Depressed Patients with Major Depression DIsorder | Experimental | Not described Receives: Drug: Scopolamine Nasal Spray |
| Depressed Patients with Bipolar Disorder | Experimental | Not described Receives: Drug: Scopolamine Nasal Spray |
| Healthy Control | Experimental | Not described Receives: Drug: Scopolamine Nasal Spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the antidepressant effects of the antimuscarinic agent scopolamine
Measured: 5 to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2003 (estimated)
- Study start27 Feb 2003
- Primary completion2 Feb 2015
- Study completion2 Feb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mood DisordersStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Carlos A Zarate, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00055575
- Sponsor's protocol ID
- 030108
- Other IDs
- 03-M-0108
- Status last verified
- 2 Feb 2015
- First submitted
- 6 Mar 2003
- Last updated
- 22 Mar 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ. Selective attention to emotional stimuli in a verbal go/no-go task: an fMRI study. Neuroreport. 2000 Jun 5;11(8):1739-44. doi: 10.1097/00001756-200006050-00028.
PubMed 10852235Murphy FC, Sahakian BJ, Rubinsztein JS, Michael A, Rogers RD, Robbins TW, Paykel ES. Emotional bias and inhibitory control processes in mania and depression. Psychol Med. 1999 Nov;29(6):1307-21. doi: 10.1017/s0033291799001233.
PubMed 10616937Murray LA, Whitehouse WG, Alloy LB. Mood congruence and depressive deficits in memory: a forced-recall analysis. Memory. 1999 Mar;7(2):175-96. doi: 10.1080/741944068.
PubMed 10645378Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA Jr. Potential of pretreatment neural activity in the visual cortex during emotional processing to predict treatment response to scopolamine in major depressive disorder. JAMA Psychiatry. 2013 Mar;70(3):280-90. doi: 10.1001/2013.jamapsychiatry.60.
PubMed 23364679
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholinergic Modulation of Cognition and Emotion in Mood Disorders: Functional Neuroimaging Studies
- ClinicalTrials.gov ID
- NCT00055575
- Acronym / sponsor ID
- 030108
- Conditions
- Mood Disorders, Healthy, Unipolar Depression, Bipolar Depression
- Keywords
- Scopolamine, Depression, fMRI, Cognition, Emotion, Brain, Bipolar Disorder, Major Depressive Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 197 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 27 Feb 2003
- Primary completion
- 2 Feb 2015 (actual)
- Study completion
- 2 Feb 2015 (actual)
- First posted
- 6 Mar 2003 (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.
This study looks at the role of a specific brain chemical system in the mood and attention symptoms seen in major depression and bipolar disorders using functional brain imaging.
Detailed description
- Objective The goal of this research project is to evaluate the role of the cholinergic system in behavioral and cognitive symptoms observed in mood disorders in humans, using functional brain neuroimaging techniques. Specific aspects of behavior and cognition are impaired in mood disorders, including selective attention, set-shifting and memory; and there is also evidence that depressed subjects exhibit a mood congruent processing bias whereby they more readily process negatively toned information as compared to positively toned information. This cognitive pattern lends itself to evaluation with functional brain imaging, both in terms of identifying the anatomical correlates of the specific behavioral and cognitive deficits as well as characterizing the effects of pharmacological manipulation. Attention and memory functions are closely tied to the cholinergic neurotransmitter system. The cholinergic system is one of the neurotransmitter systems implicated in the pathophysiology of mood disorders. Evidence suggests that during major depressive episodes, the cholinergic system is hypersensitive to acetylcholine. Agents that enhance muscarinic cholinergic receptor function increase depressive symptoms in depressed subjects, and can produce symptoms of depression in healthy subjects. The preclinical literature more specifically implicates the muscarinic receptors and indicates that the use of muscarinic antagonists, in the context of animal models of depression, results in improvement in the behavioral analogs of depression.
- Study Population The accrual ceiling for this protocol is 388 participants. 143 currently depressed patients with major depressive disorder, 100 currently depressed patients with bipolar disorder, and 145 healthy controls will participate in this study.
- Design The antimuscarinic agent, scopolamine, will be administered in a double-blind, placebo controlled manner across all studies. Clinical ratings, cognitive tasks and neuroimaging will be conducted at various timepoints to evaluate the clinical effects of scopolamine on depression, to assess the acute mood response to scopolamine; and to study the neurobiological correlates of the clinical and behavioral drug effects.
- Outcome Measures
The proposed inpatient or outpatient project investigates the role of cholinergic neurotransmission in the behavioral and cognitive symptoms observed in the depressed phase of both major depressive disorder (MDD) and bipolar disorder (BD). The studies proposed here will identify anatomical correlates of the mood congruent processing bias, working memory, attention and set-shifting deficits observed in depressed subjects. Further, these studies will evaluate the effects of the cholinergic antagonist, scopolamine, both on the performance deficits and on neural activity in brain regions recruited as subjects perform these tasks.
Dose escalation studies will be conducted to determine if higher doses of scopolamine will increase the antidepressant response rate in patients with major depressive disorder. Based on earlier work showing the predictive value in baseline neuroimaging data to predict treatment outcome, we will stratify participants at baseline into groups based on expected response to scopolamine treatment.
This approach is expected to reveal how neuromodulators influence processing in brain structures recruited to perform these tasks, both in healthy subjects and in major depressive disorders. The combined use of functional brain imaging and pharmacological manipulation to evaluate the role of neurotransmitter dysfunction in depression may direct us to potential therapeutic approaches.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Depressed Patients with Major Depression DIsorder | Experimental | Drug: Scopolamine Nasal Spray |
| Depressed Patients with Bipolar Disorder | Experimental | Drug: Scopolamine Nasal Spray |
| Healthy Control | Experimental | Drug: Scopolamine Nasal Spray |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Age 18-55
- Current diagnosis of MDD, as defined by DSM-IV criteria for recurrent MDD
- Current depressive episode
- Current IDS score in the moderately-to-severely depressed range
- Right handed
Key exclusion criteria (30 listed)
- Serious suicidal ideation or behavior (with a current plan or intent), or current delusions or hallucinations
- Medical or neurological illnesses likely to affect physiology or anatomy
- History of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria)
- Current or past history of other axis I disorders that preceded the onset of MDD or BD
- Current pregnancy (documented by pregnancy testing within 24 hours prior to pilot studies and 24 hours prior to scanning)
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 |
|---|---|---|
| Scopolamine Nasal Spray | Drug | Depressed Patients with Bipolar Disorder, Depressed Patients with Major Depression DIsorder, Healthy Control |
Primary outcome
Evaluation of the antidepressant effects of the antimuscarinic agent scopolamine
Time frame: 5 to 10 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2021.
- Background: PubMed 10852235Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ. Selective attention to emotional stimuli in a verbal go/no-go task: an fMRI study. Neuroreport. 2000 Jun 5;11(8):1739-44. doi: 10.1097/00001756-200006050-00028.
- Background: PubMed 10616937Murphy FC, Sahakian BJ, Rubinsztein JS, Michael A, Rogers RD, Robbins TW, Paykel ES. Emotional bias and inhibitory control processes in mania and depression. Psychol Med. 1999 Nov;29(6):1307-21. doi: 10.1017/s0033291799001233.
- Background: PubMed 10645378Murray LA, Whitehouse WG, Alloy LB. Mood congruence and depressive deficits in memory: a forced-recall analysis. Memory. 1999 Mar;7(2):175-96. doi: 10.1080/741944068.
- Derived from this study: PubMed 23364679Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA Jr. Potential of pretreatment neural activity in the visual cortex during emotional processing to predict treatment response to scopolamine in major depressive disorder. JAMA Psychiatry. 2013 Mar;70(3):280-90. doi: 10.1001/2013.jamapsychiatry.60.
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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.
Carlos A Zarate, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Scopolamine Nasal Spray in people with Mood Disorders and Healthy, run by National Institute of Mental Health (NIMH) 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 18 inclusion and 30 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: stopped early, as of the sponsor's last update on 22 Mar 2021. 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. 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?
The study was stopped early. 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?
Evaluation of the antidepressant effects of the antimuscarinic agent scopolamine (time frame: 5 to 10 years). 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 NCT00055575, which also lists 4 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 22 Mar 2021.