The Antidepressant Efficacy of the Anticholinergic Scopolamine
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|ClinicalTrials.gov Identifier: NCT00369915|
Recruitment Status : Terminated
First Posted : August 30, 2006
Results First Posted : April 29, 2016
Last Update Posted : November 10, 2016
|First Submitted Date ICMJE||August 29, 2006|
|First Posted Date ICMJE||August 30, 2006|
|Results First Submitted Date||April 11, 2014|
|Results First Posted Date||April 29, 2016|
|Last Update Posted Date||November 10, 2016|
|Study Start Date ICMJE||August 2006|
|Actual Primary Completion Date||January 2013 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Change in Depression Severity [ Time Frame: Outcome measures obtained at each of 12 sessions ]
The Montgomery-Asberg Depression Rating Scale (MADRS) has a range of scores from 0 to 60 where the highest values indicate the most depression.
|Original Primary Outcome Measures ICMJE
||Change in Depression Severity|
|Change History||Complete list of historical versions of study NCT00369915 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Hamilton Anxiety Rating Scale [ Time Frame: Each of 12 sessions. ]
The Hamilton Anxiety Rating Scale (HARS) has a range of scores from 0 to 56 where the highest values indicate the most anxiety.
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||The Antidepressant Efficacy of the Anticholinergic Scopolamine|
|Official Title ICMJE||The Antidepressant Efficacy of the Anticholinergic Scopolamine|
|Brief Summary||A previous study showed that the intravenous administration of scopolamine produces antidepressant effects. This study is designed to determine if other routes of administration of scopolamine produce antidepressant effects.|
Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Moreover, in those patients who do experience symptomatic relief following conventional anti-depressant treatment, clinical improvement is not evident for 3-4 weeks. Thus, there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression.
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 individuals. 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.
Preliminary results obtained under protocol 3-M-0108 provide strong evidence for the potential effectiveness of the anticholinergic scopolamine in rapidly producing clinically significant antidepressant effects. We observed large reductions in Montgomery-Asberg Depression Rating Scale (MADRS) scores that occurred over hours/days following i.v. infusion of scopolamine, which stood in marked contrast to the 3-4 week period generally required for conventional therapies. Moreover, these improvements were observed in subjects who had been nonresponsive or incompletely responsive to conventional antidepressant therapies, highlighting the potential for this treatment to benefit a larger percentage of individuals with depression. The goal of this research project is to perform a clinical trial to evaluate the efficacy of the muscarinic cholinergic receptor antagonist scopolamine administered via transdermal patch on clinical symptoms of depression.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Scopolamine|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Terminated|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date||January 2013|
|Actual Primary Completion Date||January 2013 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Two groups of subjects will be recruited for studies under this protocol: unipolar depressives and bipolar depressives. Subjects with unipolar or bipolar depression appear to exhibit abnormal cholinergic function during the depressed phase, and no differences are hypothesized to exist between MDD and BD depressives herein. However, while BD subjects are more difficult to recruit, the evidence for cholinergic abnormalities has been particularly compelling for BD. Moreover, observations from our pilot study suggest that scopolamine will improve symptoms in both MDD and BD, a particularly persuasive observation given BD notoriously has been difficult to treat. Thus, the magnitude of this serious clinical problem justifies the inclusion of BD subjects. Therefore both groups will be recruited. However, BD Type I subjects will be included only if they are currently stable on lithium or valproate to reduce the risks associated with possible precipitation of mania.
The presence of inclusion and exclusion criteria will be established using both an unstructured clinical interview with a psychiatrist and the Structured Clinical Interview for DSM-IV (SCID). Family history of mental illness will be obtained from the subject using the Family Interview of Genetic Studies. We will recruit 24 subjects per group.
DEPRESSED SAMPLES: Subjects (ages 18-55) currently suffering from a major depressive episode falling into one of the following subgroups:
Subjects will be recruited who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine) prior to screening. Subjects also will be excluded if they have: a) serious suicidal ideation or behavior, or current delusions or hallucinations, b) inability to provide informed consent, c) serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, endocrinologic, neurologic, immunologic, or hematologic disease, d) a history of drug or alcohol abuse within 6 months or alcohol or drug dependence in the last five years (DSM IV criteria), e) not using a medically accepted means of contraception and are a woman of childbearing potential, f) current pregnancy (documented by pregnancy testing prior to each brain scan to avoid exposing a fetus to radiation or to a research MRI scan that is not medically necessary), g) current breast feeding, h) history of ulcerative colitis or toxic megacolon, i) vision and/or hearing problems severe enough to interfere with testing, j) electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction, k) current blood pressure of greater than 160 mm Hg or less than 90 mm Hg systolic, or greater than 90 mm Hg diastolic, l) clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, clinic evidence of cerebrovascular disease, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncracy to anticholinergic agents (e.g. skin rashes), glaucoma, renal or hepatic impairment, m) current nicotine use or nicotine dependence within last six months (due to the effects of nicotine on the cholinergic system) n) narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine) o) age greater than 55 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), p) exposure within two weeks to medications likely to affect mood or cognition or likely to interact with scopolamine (e.g. narcotics or anti-cholinergic agents)- as verified by history and urine drug screen, q) HIV positive status, r) history of gastric or intestinal obstructions, s) history of urinary retention or bladder obstruction. During the course of this study, participants will be unable to take some medications, including antidepressant or antianxiety agents, sleep aids, diphenhydramine (e.g. Benedryl) or cough/cold preparations that contain diphenhydramine or antihistamines. A detailed list of allowed and not allowed medications is provided in Appendix B in the protocol.
We are not excluding comorbid anxiety disorders. Exclusion of patients with comorbid anxiety disorders would affect the generalizability of our findings since a substantial percentage of patients with major depression have these comorbid diagnoses. Instead, we will exclude patients with this comorbid diagnosis only if it is believed to be of clinical significance. Allowing participation by patients with histories of comorbid anxiety disorders broadens the inclusion criteria to more closely approximate patients seen in real world settings.
|Ages||18 Years to 55 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00369915|
|Other Study ID Numbers ICMJE||060234
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP