Effects of Intravenous (IV) Citalopram on Emotional Brain Activity in Healthy Young and Elderly Adults

Sponsor

Rotman Research Institute at Baycrest (Other)

Overall Status

Terminated

CT.gov ID

NCT01216449

Collaborator

Centre for Addiction and Mental Health (Other), University of Toronto (Other)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) are most commonly prescribed to treat depression and anxiety. How antidepressants work on the brain to alter mood and behaviour is not well understood. This study will use a brain scanning technique (functional magnetic resonance imaging) to examine how aging impacts brain activation during emotional tasks after the administration of intravenous (IV) citalopram (this is the only SSRI available in this form, and is well tolerated and safe in young and old adults). The investigators will further determine what role genetic differences play in this relationship. The investigators expect to see an increase in brain signal as the concentration of IV citalopram increases. However, the investigators propose that the brain signal in older adults will not be as strong as in younger adults. Furthermore, the investigators expect that participants genetically predisposed to have fewer serotonin transporters (the site of action of SSRIs) will show greater decreases in brain activation with citalopram.

Condition or Disease	Intervention/Treatment	Phase
Healthy Young and Elderly Volunteers	Drug: Intravenous Citalopram Drug: Normal Saline	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

Pharmacodynamics of Intravenous Citalopram in the Elderly: a Functional Magnetic Resonance Imaging Analysis

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous Citalopram	Drug: Intravenous Citalopram Single dose of 20mg parenteral citalopram diluted in 250mL of 0.9% sodium chloride solution, infused over 30 minutes
Placebo Comparator: Normal Saline 250mL of 0.9% Sodium Chloride Solution	Drug: Normal Saline Single dose of 250mL of 0.9% sodium chloride solution, infused over 30 minutes

Arm

Intervention/Treatment

Experimental: Intravenous Citalopram

Drug: Intravenous Citalopram

Single dose of 20mg parenteral citalopram diluted in 250mL of 0.9% sodium chloride solution, infused over 30 minutes

Placebo Comparator: Normal Saline

250mL of 0.9% Sodium Chloride Solution

Drug: Normal Saline

Single dose of 250mL of 0.9% sodium chloride solution, infused over 30 minutes

Outcome Measures

Primary Outcome Measures

BOLD fMRI Response [Visit 1, Visit 2]
Changes in affect-related neuronal activation as measured by blood oxygenation level-dependent (BOLD) fMRI response to IV citalopram are the primary outcome measures. Imaging data will be compared between IV citalopram and placebo administration and young and old adults.

Secondary Outcome Measures

Genetics and Cognitive/Emotional Change [Visit 1, Visit 2]
Secondary measures include analysis of the relationship between 5HTT polymorphism and neuronal activation, and changes in cognitive and emotional assessments between IV citalopram and placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male aged 60 or older (elderly group)
Male aged 20-40 (younger adult group)
English speaking
Right-handed
Non-smoker
Score of 27 or greater on the Mini Mental State Exam

Exclusion Criteria:

Unstable medical, cardiac, or neurological illness (including stroke, brain tumour, epilepsy, significant head injury, Alzheimer's, Parkinson's or Huntington's disease)
Laboratory results indicating unanticipated illness or intolerability of blood drawing procedures or of study drug
Current or lifetime Axis-I psychiatric diagnosis on the DSM-IV/SCID (i.e., Module A: Mood, Module F: Anxiety, Module B & C: Psychosis)
History of drug or alcohol abuse within one year, or lifetime history of alcohol or drug dependence (i.e., SCID Module E: Substance Abuse, or clinically significant urine toxicology screen)
History of non-tolerance to SSRI therapy; including history of SSRI-related syndrome of inappropriate antidiuretic hormone secretion (SIADH) or sinus bradycardia on ECG (less than 50 beats per minute)
Contraindication to MRI (as per MRI Contraindication Screening Form)