Modafinil's Effects on Cognition in Remitted MDD

NCT03620253 | Terminated Phase 3

• 1 other identifier: MOCOG-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive difficulties such as indecisiveness or inability to concentrate are core symptoms of depression with up to 90% of untreated depressed individuals experiencing these symptoms. As many as half of those who remit from a major depressive episode continue to experience residual cognitive deficits, but these symptoms are frequently overlooked in clinical practice. This leads to persistent cognitive deficits which can cause reduced level of functioning and loss of productivity. As standard antidepressants have an inadequate impact on these residual cognitive symptoms, further treatment options are required. Modafinil is a wakefulness agent with evidence that it improves some domains in cognition such as memory in those whose non-cognitive depressive symptoms have been treated over a short term period. This medication may have favourable lasting effects on cognition, such as the ability to plan and execute tasks in those who receive modafinil for a longer time period. The aim of this study is to investigate whether modafinil can enhance cognition and have additional effects on functioning and work productivity in a sample of participants who were treated for depression but who continue to experience cognitive deficits.

Conditions

Major Depressive Disorder; Cognitive Impairment

Keywords

modafinil; remitted depression; cognition

Outcome Measures

Primary Outcomes (1)

• Cognition

  Cognition will be measured using a Neurocognitive Index, which will be calculated using the CNS Vital Signs Neurocognitive Battery (a computer program). The domains tested within the cognitive battery include composite memory, psychomotor speed, reaction time, complex attention, cognitive flexibility, and processing speed. The Neurocognitive Index is based on a composite, average score of the scores on these 6 domains. From the Neurocognitive Index score, the CNS Vital Signs program classifies the participant as above, average, low average, low, or very low based on their deviation from a standard score of 85.

  8 weeks

Secondary Outcomes (10)

• Composite Memory

  8 weeks

• Psychomotor Speed

  8 weeks

• Reaction Time

  8 weeks

• Complex Attention

  8 weeks

• Cognitive Flexibility

  8 weeks

Other Outcomes (9)

• Overall Quality of Life

  8 weeks

• Life Enjoyment and Satisfaction

  8 weeks

• Sleepiness

  8 weeks

Study Arms (2)

Modafinil

EXPERIMENTAL

Participants will be administered 100 mg modafinil tablets, that will be over-encapsulated, for one week. If the drug is well tolerated, the dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning.

Drug: Modafinil

Placebo

PLACEBO COMPARATOR

Participants will be administered 100 mg placebo capsule. This capsule will have all the same ingredients as the modafinil tablets, minus the active ingredient. After 1 week, participants' dosage will be increased to 200 mg for the remaining 7 weeks of the study. Capsules are taken daily in the morning.

Drug: Placebo

Interventions

Modafinil DRUG

Participants randomized to the modafinil group will receive 100 mg of modafinil capsules for 1 week, followed by 200 mg for 7 weeks (as long as the drug is well tolerated), which they will take daily in the morning. During this time, participants will complete questionnaires and neurocognitive tests, and report adverse events at study visits.

Also known as: Provigil, Alertec, 2-benzhydrylsulfinylacetamide

Modafinil

Placebo DRUG

Participants randomized to the placebo group will receive 100 mg placebo capsules for 1 week, followed by 200 mg for 7 weeks, which they will take daily in the morning. During this time, participants will complete questionnaires and neurocognitive tests, and report adverse events at study visits.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnostic and Statistical Manual (DSM)-5 criteria for past Major Depressive Episode within MDD, confirmed through Mini-International Neuropsychiatric Interview (MINI) diagnosis
• Age between 18 and 55 years
• Montgomery-Åsberg Depression Rating Scale \< 7 (in remission)
• Ability to read and understand English
• Participant has been treated with an antidepressant for ≥ 6 months prior to enrolment
• Participant agrees to remain on a stable antidepressant regimen for the duration of the trial (8 weeks)
• Participant is currently experiencing cognitive deficits, as confirmed by an NCI \>1 standard deviation below the mean on CNS Vital Signs cognitive battery
• Women of child bearing potential must agree to use birth control for the duration of the study and 1 month following discontinuation of the study drug

You may not qualify if:

• Pregnancy/lactation
• Lifetime history of Bipolar I, II or psychosis; other comorbidities (e.g. Generalized Anxiety, Panic Disorder) may be allowed by clinician judgement
• Subject has current clinical diagnosis of autism, dementia, intellectual disability, or mild cognitive impairment
• Meets DSM-5 criteria for active Post-Traumatic Stress Disorder, confirmed through MINI diagnosis
• Subject meets criteria for current personality disorder
• Concomitant use of monoamine oxidase inhibitors and/or other psychotropic drugs including lithium, clomipramine, and triazolam
• Recent (\< 6 months) stimulant use, such as medications used for attention deficit hyperactivity disorder
• Subject is taking antipsychotics
• Subject is taking herbaceuticals (i.e. natural products that have psychoactive properties, such as St. John's wort)
• Concomitant use of medications that may interact with modafinil, including warfarin and cyclosporine
• Medical condition requiring immediate investigation or treatment
• Recent (\< 6 months)/current history of drug abuse/dependence (other than caffeine or nicotine)
• Previous intolerance or failure to respond to an adequate trial of modafinil
• Any past history of head injury or concussion, as confirmed by the Ohio State University Traumatic brain injury (TBI) Identification Short Form
• Current suicidal ideation (MADRS Item 10 ≤2 or by clinician judgement)

Sponsors & Collaborators

• Unity Health Toronto: lead
• Ontario Ministry of Health and Long Term Care: collaborator
• The Canadian Biomarker Integration Network in Depression: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B1M4, Canada

Location

Related Publications (11)

• Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.

  PMID: 12813115 BACKGROUND

• Woo YS, Rosenblat JD, Kakar R, Bahk WM, McIntyre RS. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients. Clin Psychopharmacol Neurosci. 2016 Feb 29;14(1):1-16. doi: 10.9758/cpn.2016.14.1.1.

  PMID: 26792035 BACKGROUND

• McIntyre RS, Cha DS, Soczynska JK, Woldeyohannes HO, Gallaugher LA, Kudlow P, Alsuwaidan M, Baskaran A. Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress Anxiety. 2013 Jun;30(6):515-27. doi: 10.1002/da.22063. Epub 2013 Mar 6.

  PMID: 23468126 BACKGROUND

• Bhalla RK, Butters MA, Mulsant BH, Begley AE, Zmuda MD, Schoderbek B, Pollock BG, Reynolds CF 3rd, Becker JT. Persistence of neuropsychologic deficits in the remitted state of late-life depression. Am J Geriatr Psychiatry. 2006 May;14(5):419-27. doi: 10.1097/01.JGP.0000203130.45421.69.

  PMID: 16670246 BACKGROUND

• Salagre E, Sole B, Tomioka Y, Fernandes BS, Hidalgo-Mazzei D, Garriga M, Jimenez E, Sanchez-Moreno J, Vieta E, Grande I. Treatment of neurocognitive symptoms in unipolar depression: A systematic review and future perspectives. J Affect Disord. 2017 Oct 15;221:205-221. doi: 10.1016/j.jad.2017.06.034. Epub 2017 Jun 19.

  PMID: 28651185 BACKGROUND

• Lam RW, Kennedy SH, Mclntyre RS, Khullar A. Cognitive dysfunction in major depressive disorder: effects on psychosocial functioning and implications for treatment. Can J Psychiatry. 2014 Dec;59(12):649-54. doi: 10.1177/070674371405901206. No abstract available.

  PMID: 25702365 BACKGROUND

• Hasselbalch BJ, Knorr U, Kessing LV. Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review. J Affect Disord. 2011 Nov;134(1-3):20-31. doi: 10.1016/j.jad.2010.11.011. Epub 2010 Dec 15.

  PMID: 21163534 BACKGROUND

• Rock PL, Roiser JP, Riedel WJ, Blackwell AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med. 2014 Jul;44(10):2029-40. doi: 10.1017/S0033291713002535. Epub 2013 Oct 29.

  PMID: 24168753 BACKGROUND

• Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology. 2008 Jun;33(7):1477-502. doi: 10.1038/sj.npp.1301534. Epub 2007 Aug 22.

  PMID: 17712350 BACKGROUND

• DeBattista C, Lembke A, Solvason HB, Ghebremichael R, Poirier J. A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol. 2004 Feb;24(1):87-90. doi: 10.1097/01.jcp.0000104910.75206.b9.

  PMID: 14709953 BACKGROUND

• Kaser M, Deakin JB, Michael A, Zapata C, Bansal R, Ryan D, Cormack F, Rowe JB, Sahakian BJ. Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Mar;2(2):115-122. doi: 10.1016/j.bpsc.2016.11.009.

  PMID: 28299368 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Cognitive Dysfunction

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Sidney H Kennedy, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 25 participants will be randomly assigned to the modafinil treatment group, and 25 to the placebo group. The drug/placebo will be randomized and dispensed by the research pharmacy at St. Michael's Hospital. A research technician who is blind to the study will prepare the capsules and break the blind at the end of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Psychiatrist

Model Details: 50 Participants (aged 18-55) who are experiencing cognitive deficits (measured as Neurocognitive Index \>1 standard deviation below the mean) despite remission from depression (Montgomery-Asberg Rating Scale for Depression (MADRAS) score \<7) will be eligible to receive modafinil (100-200mg daily) or two identical placebo capsules each morning for a period of 8 weeks.

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: August 8, 2018
• Study Start: October 15, 2018
• Primary Completion: August 6, 2019
• Study Completion: August 6, 2019
• Last Updated: August 8, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)