The Role of Serotonin in Compulsive Behavior in Humans: Underlying Brain Mechanisms
NCT ID: NCT04336228
Last Updated: 2024-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE4
46 participants
INTERVENTIONAL
2020-04-01
2027-12-31
Brief Summary
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* The status of the central serotonin (5-hydroxytryptamine, 5-HT) system in compulsive behaviour and how it is affected by sub-chronic escitalopram administration
* The mechanisms underlying how sub-chronic administration of escitalopram affects the central 5-HT system
* How changes in cognitive performance, including the balance between habitual and goal-directed mechanisms, are affected in compulsive behaviour by boosting 5-HT function
* How functional brain changes in cognitive function measured with magnetic resonance imaging relate to altered 5-HT function following escitalopram administration.
Detailed Description
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A number of behavioural and cognitive features of OCD, including endophenotype markers that appear to characterise the disorder have been determined. These include a shift in cognitive control from a goal-directed strategy to a habitual (stimulus-response, S-R) strategy, cognitive rigidity in terms of both reversal learning and attentional set-shifting, impaired response inhibition and planning, and a tendency to over-respond to spurious negative feedback in a probabilistic learning paradigm. Neural substrates of these deficits are being investigated using brain imaging methodologies based on magnetic resonance and preliminary evidence suggests an over-active medial prefrontal cortex-caudate nucleus circuits and underactive lateral prefrontal cortex-putamen circuits. However, little evidence exists that relates to the hypothesis of an over-active habit system in this disorder or to the role of serotonin in all these cognitive and behavioural deficits observed in OCD and compulsivity in general.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
BASIC_SCIENCE
TRIPLE
Study Groups
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Healthy Control Group
The healthy placebo control group will be administered the exact same procedure as the intervention group, the only difference being that this group will be administered a placebo tablet.
Placebo oral tablet
20mg placebo tablet daily for 3-4 weeks.
Obsessive-Compulsive Disorder / High Compulsivity Control Group
The OCD/high compulsivity placebo control group will be administered the exact same procedure as the intervention group, the only difference being that this group will be administered a placebo tablet.
Placebo oral tablet
20mg placebo tablet daily for 3-4 weeks.
Healthy Intervention Group
The healthy intervention group will be administered 20mg of Escitalopram daily for 3-4 weeks.
Escitalopram
20mg daily for 3-4 weeks.
Obsessive-Compulsive Disorder / High Compulsivity Intervention Group
The OCD/high compulsivity intervention group will be administered 20mg of Escitalopram daily for 3-4 weeks.
Escitalopram
20mg daily for 3-4 weeks.
Interventions
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Escitalopram
20mg daily for 3-4 weeks.
Placebo oral tablet
20mg placebo tablet daily for 3-4 weeks.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* Non- fluent in Danish or pronounced visual or auditory impairments
* Current or past learning disability.
* Pregnancy
* Lactation
* Participation in experiments with radioactivity (\> 10 mSv) within the last year or significant occupational exposure to radioactivity.
* Contraindications for MRI (pacemaker, metal implants, etc.).
* Allergy to the ingredients in the administered drug.
* Abnormal ECG (e.g. prolonged QT syndrome).
* Dizzy when changing from supine to upright position (e.g. postural orthostatic tachycardia syndrome).
* Mild hypotension (blood pressure below 100/70 mmHg) or hypertension (blood pressure above 140/90 mmHg).
* Head injury or concussion resulting in loss of consciousness for more than 2 min.
* Alcohol or drug abuse
* Drug use other than tobacco and alcohol within the last 30 days.
* Hash \> 50 x lifetime.
* Drugs \> 10 x lifetime (for each substance).
* Current medication with serotonergic acting compounds. Use of other psychoactive substances must be stable at least one month prior to inclusion and maintained throughout the study.
* Severe physical impairments affecting eyesight or motor performance.
* For the OCD group: other Axis I mental disorder as primary diagnosis according to ICD-10 criteria.
* For healthy volunteers: any current or former primary psychiatric disorder (Axis I WHO ICD-10 diagnostic classification).
18 Years
70 Years
ALL
Yes
Sponsors
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University of Cambridge
OTHER
Lundbeck Foundation
OTHER
Rigshospitalet, Denmark
OTHER
Responsible Party
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Gitte Moos Knudsen
Professor, MD, DMSc
Principal Investigators
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Gitte M. Knudsen, Professor
Role: STUDY_CHAIR
Neurobiology Research Unit, Rigshospitalet
Locations
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Neurobiology Research Unit, Rigshospitalet
Copenhagen, , Denmark
Countries
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References
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Clarke HF, Dalley JW, Crofts HS, Robbins TW, Roberts AC. Cognitive inflexibility after prefrontal serotonin depletion. Science. 2004 May 7;304(5672):878-80. doi: 10.1126/science.1094987.
Dayan P, Huys QJ. Serotonin in affective control. Annu Rev Neurosci. 2009;32:95-126. doi: 10.1146/annurev.neuro.051508.135607.
Palminteri S, Clair AH, Mallet L, Pessiglione M. Similar improvement of reward and punishment learning by serotonin reuptake inhibitors in obsessive-compulsive disorder. Biol Psychiatry. 2012 Aug 1;72(3):244-50. doi: 10.1016/j.biopsych.2011.12.028. Epub 2012 Feb 10.
Pelloux Y, Dilleen R, Economidou D, Theobald D, Everitt BJ. Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats. Neuropsychopharmacology. 2012 Oct;37(11):2505-14. doi: 10.1038/npp.2012.111. Epub 2012 Jul 4.
Groman SM, James AS, Seu E, Crawford MA, Harpster SN, Jentsch JD. Monoamine levels within the orbitofrontal cortex and putamen interact to predict reversal learning performance. Biol Psychiatry. 2013 Apr 15;73(8):756-62. doi: 10.1016/j.biopsych.2012.12.002. Epub 2013 Jan 16.
Worbe Y, Palminteri S, Savulich G, Daw ND, Fernandez-Egea E, Robbins TW, Voon V. Valence-dependent influence of serotonin depletion on model-based choice strategy. Mol Psychiatry. 2016 May;21(5):624-9. doi: 10.1038/mp.2015.46. Epub 2015 Apr 14.
el Mansari M, Bouchard C, Blier P. Alteration of serotonin release in the guinea pig orbito-frontal cortex by selective serotonin reuptake inhibitors. Relevance to treatment of obsessive-compulsive disorder. Neuropsychopharmacology. 1995 Oct;13(2):117-27. doi: 10.1016/0893-133X(95)00045-F.
Lissemore JI, Sookman D, Gravel P, Berney A, Barsoum A, Diksic M, Nordahl TE, Pinard G, Sibon I, Cottraux J, Leyton M, Benkelfat C. Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline. Transl Psychiatry. 2018 Apr 18;8(1):82. doi: 10.1038/s41398-018-0128-4.
Banca P, Voon V, Vestergaard MD, Philipiak G, Almeida I, Pocinho F, Relvas J, Castelo-Branco M. Imbalance in habitual versus goal directed neural systems during symptom provocation in obsessive-compulsive disorder. Brain. 2015 Mar;138(Pt 3):798-811. doi: 10.1093/brain/awu379. Epub 2015 Jan 6.
Gillan CM, Papmeyer M, Morein-Zamir S, Sahakian BJ, Fineberg NA, Robbins TW, de Wit S. Disruption in the balance between goal-directed behavior and habit learning in obsessive-compulsive disorder. Am J Psychiatry. 2011 Jul;168(7):718-26. doi: 10.1176/appi.ajp.2011.10071062. Epub 2011 May 15.
Apergis-Schoute AM, Gillan CM, Fineberg NA, Fernandez-Egea E, Sahakian BJ, Robbins TW. Neural basis of impaired safety signaling in Obsessive Compulsive Disorder. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3216-3221. doi: 10.1073/pnas.1609194114. Epub 2017 Mar 6.
Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006 Jul;163(7):1282-4. doi: 10.1176/ajp.2006.163.7.1282.
Chamberlain SR, Fineberg NA, Menzies LA, Blackwell AD, Bullmore ET, Robbins TW, Sahakian BJ. Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Feb;164(2):335-8. doi: 10.1176/ajp.2007.164.2.335.
Vaghi MM, Vertes PE, Kitzbichler MG, Apergis-Schoute AM, van der Flier FE, Fineberg NA, Sule A, Zaman R, Voon V, Kundu P, Bullmore ET, Robbins TW. Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity. Biol Psychiatry. 2017 Apr 15;81(8):708-717. doi: 10.1016/j.biopsych.2016.08.009. Epub 2016 Aug 11.
Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989 Nov;46(11):1012-6. doi: 10.1001/archpsyc.1989.01810110054008.
Haahr ME, Fisher PM, Jensen CG, Frokjaer VG, Mahon BM, Madsen K, Baare WF, Lehel S, Norremolle A, Rabiner EA, Knudsen GM. Central 5-HT4 receptor binding as biomarker of serotonergic tonus in humans: a [11C]SB207145 PET study. Mol Psychiatry. 2014 Apr;19(4):427-32. doi: 10.1038/mp.2013.147. Epub 2013 Nov 5.
Foa, E. B. et al. The validation of a new obsessive-compulsive disorder scale: The obsessive-compulsive inventory. Psychological Assessment 10(3), 206-214, 1998.
Provided Documents
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Document Type: Statistical Analysis Plan
Other Identifiers
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H-18038325
Identifier Type: -
Identifier Source: org_study_id