Cholinergic Modulation of Condition and Emotion in Mood Disorders: Functional Neuroimaging Studies

NCT00055575 | Terminated Phase 2 FDA Drug

• 2 other identifiers: 03010803-M-0108
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mood Disorders; Healthy; Unipolar Depression; Bipolar Depression

Keywords

Scopolamine; Depression; fMRI; Cognition; Emotion; Brain; Bipolar Disorder; Major Depressive Disorder; MDD; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Evaluation of the antidepressant effects of the antimuscarinic agent scopolamine

  5 to 10 years

Study Arms (3)

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

Interventions

Scopolamine Nasal Spray DRUG

Depressed Patients with Bipolar Disorder; Depressed Patients with Major Depression DIsorder; Healthy Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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)
• Current breast feeding
• 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 10852235 BACKGROUND

• Murphy 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.

  PMID: 10616937 BACKGROUND

• Murray 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.

  PMID: 10645378 BACKGROUND

• Furey 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.

  PMID: 23364679 DERIVED

MeSH Terms

Conditions

Mood Disorders; Depressive Disorder; Bipolar Disorder; Depression; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Mental Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior

Study Officials

• Carlos A Zarate, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2003
• First Posted: March 6, 2003
• Study Start: February 27, 2003
• Primary Completion: February 2, 2015
• Study Completion: February 2, 2015
• Last Updated: March 22, 2021

Record last verified: 2015-02-02

Locations

US (1)