Cipralex® for Anxiety Disorders in Adolescents

Anxiety Disorder Clinical Trial

— CAP-E  

Official title:

Cipralex® for Anxiety Disorders in Adolescents: Clinical and Physiological Changes Associated With Open Label, Flexible-dose Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01293838
• Other study ID #: IMHR REB#2007036
• Secondary ID: 123485
• Status: Recruiting
• Phase: Phase 1
• First received: February 10, 2011
• Last updated: February 10, 2011
• Start date: March 2008
• Est. completion date: January 2012

Study information

• Verified date: January 2011
• Source: University of Ottawa
• Contact: Martine Flament, MD
• Phone: 613-722-6521
• Email: martine.flament[@]rohcg.on.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The primary objective is to examine whether Cipralex® is effective and safe in the treatment of anxiety disorders in youth. The secondary objective is to identify changes in arousal and stress response from pre- to post-treatment with Cipralex® in youth with anxiety disorders.

Description:

Anxiety disorders are the most common mental illnesses of adolescence, with an overall prevalence ranging from 5.0% to 10.8% (Costello et al, 1996; Ford et al, 2003; Fergusson et al, 1993; Shaffer et al, 1996; Verhulst et al., 1997). Six- to 12-month prevalence has been estimated to be 0.5-2.4% for separation anxiety disorder (SAD), 2.1-4.6% for overanxious disorder (OAD), the DSM-III antecedent of generalized anxiety disorder (GAD), 1.7-6.9% for social phobia (SP), and 0.3-1.2% for panic disorder (PD) (Bowen et al, 1990; Fergusson et al, 1993; Ford et al, 2003; Lewinsohn et al, 1993; Romano et al, 2001; Verhulst et al, 1997). In the US National Comorbidity Survey, the median age of onset for anxiety disorders was 11 years (range 6-21 years), which was much younger than for substance use disorders (20 years) and mood disorders (30 years) (Kessler, 2005). However, anxious youth often go undiagnosed and untreated, possibly because they tend to be compliant and nondisruptive (Esser et al, 1990). This is of concern since research suggests that youth with untreated anxiety disorders are more likely to develop significant problems later in life, such as continued anxiety, depression, substance abuse, suicide attempts, educational underachievement, and impaired psychosocial functioning (Pine et al, 1998; Woodward & Fergusson, 2001).

The existing literature on pharmacological treatment of anxiety disorders in adolescents is limited, but suggests that the selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for pervasive and impairing anxiety disorders in youth (Reinblatt & Walkup, 2005). A few randomized controlled trials (RCT) provide support for the use of SSRIs such as fluvoxamine and fluoxetine for the treatment of SAD, GAD and SP. Cipralex® is a newer SSRI whose use for treatment of anxiety disorders in adolescents has been documented in only one previous open trial (Isolan et al., 2007). Results from this study and a few RCTs conducted in adults with anxiety disorders suggest that Cipralex® should be effective and safe for relieving symptoms of anxiety in adolescents.

Primary objectives: (1) to assess the clinical and psychosocial changes associated with 16-week open-label treatment with Cipralex® (10 to 20 mg/day) in adolescents with SAD, SP, PD and/or GAD; (2) to assess the tolerance and safety of Cipralex® (10 to 20 mg/day for 16 weeks) in adolescents with SAD, SP, PD and/or GAD.

Secondary objective: (1) to investigate changes in physiological measures of arousal and stress response (i.e., heart rate variability, salivary concentrations of cortisol and alpha-amylase, acoustic startle response,) using standardized laboratory stressors, before and after treatment with Cipralex® (10 to 20 mg/day for 16 weeks) in youth with anxiety disorders.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 18 Years

Eligibility

Inclusion Criteria:

• Primary diagnosis of (1 or more)

• Social Phobia

• Generalized Anxiety Disorder

• Separation Anxiety Disorder

• Panic Disorder

• Comorbid depression allowed

Exclusion Criteria:

• Unstable medical condition

• Substance use disorder

• Current diagnosis of OCD

• Lifetime diagnosis of developmental delay, pervasive developmental disorder, psychosis

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Disease

Intervention

Drug:
• Cipralex®
Based on a starting rate of 5 mg/day, increased by 5 mg every 2 weeks to a maximum of 20 mg/day for weeks 7-16, each participant will receive up to: 10 mg tablets: 28 20 mg tablets: 84 Total for 30 participants: 10 mg tablets: 840 20 mg tablets: 2520 Continuation study for participants who respond to Cipralex - Across 12 weeks, each participant will receive up to: *20 mg tablets: 84 Total for continuation study for all participants (assuming a 60% response rate, N=18): *20 mg tablets: 1512

Locations

Country	Name	City	State
Canada	The University of Ottawa Institute of Mental Health Research	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University of Ottawa	H. Lundbeck A/S

Country where clinical trial is conducted

Canada, 

References & Publications (21)

Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the Beck Depression Inventory-2. San Antonio, TX: Psychological Corporation.

Bowen RC, Offord DR, Boyle MH. The prevalence of overanxious disorder and separation anxiety disorder: results from the Ontario Child Health Study. J Am Acad Child Adolesc Psychiatry. 1990 Sep;29(5):753-8. — View Citation

Costello EJ, Angold A, Burns BJ, Stangl DK, Tweed DL, Erkanli A, Worthman CM. The Great Smoky Mountains Study of Youth. Goals, design, methods, and the prevalence of DSM-III-R disorders. Arch Gen Psychiatry. 1996 Dec;53(12):1129-36. — View Citation

Epstein, M. H., & Sharma, J. M. (2004). Behavioral and Emotional Rating Scale-2: A strength-based approach to assessment. Austin, TX: PRO-ED.

Esser G, Schmidt MH, Woerner W. Epidemiology and course of psychiatric disorders in school-age children--results of a longitudinal study. J Child Psychol Psychiatry. 1990 Jan;31(2):243-63. — View Citation

Fergusson DM, Horwood LJ, Lynskey MT. Prevalence and comorbidity of DSM-III-R diagnoses in a birth cohort of 15 year olds. J Am Acad Child Adolesc Psychiatry. 1993 Nov;32(6):1127-34. — View Citation

Guy, W. & ECDEU (1976). Assessment Manual for Psychopharmacology. Early Clinical Drug Evaluation Unit.

Isolan L, Pheula G, Salum GA Jr, Oswald S, Rohde LA, Manfro GG. An open-label trial of escitalopram in children and adolescents with social anxiety disorder. J Child Adolesc Psychopharmacol. 2007 Dec;17(6):751-60. doi: 10.1089/cap.2007.0007. — View Citation

Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun;62(6):593-602. Erratum in: Arch Gen Psychiatry. 2005 Jul;62(7):768. Merikangas, Kathleen R [added]. — View Citation

Lewinsohn PM, Hops H, Roberts RE, Seeley JR, Andrews JA. Adolescent psychopathology: I. Prevalence and incidence of depression and other DSM-III-R disorders in high school students. J Abnorm Psychol. 1993 Feb;102(1):133-44. Erratum in: J Abnorm Psychol 1993 Nov;102(4):517. — View Citation

March JS, Parker JD, Sullivan K, Stallings P, Conners CK. The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity. J Am Acad Child Adolesc Psychiatry. 1997 Apr;36(4):554-65. — View Citation

Pine DS, Cohen P, Gurley D, Brook J, Ma Y. The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry. 1998 Jan;55(1):56-64. — View Citation

Posner K, Melvin GA, Stanley B, Oquendo MA, Gould M. Factors in the assessment of suicidality in youth. CNS Spectr. 2007 Feb;12(2):156-62. — View Citation

Reinblatt SP, Walkup JT. Psychopharmacologic treatment of pediatric anxiety disorders. Child Adolesc Psychiatr Clin N Am. 2005 Oct;14(4):877-908, x. Review. — View Citation

Romano E, Tremblay RE, Vitaro F, Zoccolillo M, Pagani L. Prevalence of psychiatric diagnoses and the role of perceived impairment: findings from an adolescent community sample. J Child Psychol Psychiatry. 2001 May;42(4):451-61. — View Citation

Shaffer D, Fisher P, Dulcan MK, Davies M, Piacentini J, Schwab-Stone ME, Lahey BB, Bourdon K, Jensen PS, Bird HR, Canino G, Regier DA. The NIMH Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3): description, acceptability, prevalence rates, and performance in the MECA Study. Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. J Am Acad Child Adolesc Psychiatry. 1996 Jul;35(7):865-77. — View Citation

Silverman, W. K. & Albano, A. M. (1996). The Anxiety Disorders Interview Schedule for DSM-IV—Child and Parent Versions. San Antonio, TX, Psychological Corporation.

The Pediatric Anxiety Rating Scale (PARS): development and psychometric properties. J Am Acad Child Adolesc Psychiatry. 2002 Sep;41(9):1061-9. — View Citation

Topolski TD, Patrick DL, Edwards TC, Huebner CE, Connell FA, Mount KK. Quality of life and health-risk behaviors among adolescents. J Adolesc Health. 2001 Dec;29(6):426-35. — View Citation

Verhulst FC, van der Ende J, Ferdinand RF, Kasius MC. The prevalence of DSM-III-R diagnoses in a national sample of Dutch adolescents. Arch Gen Psychiatry. 1997 Apr;54(4):329-36. — View Citation

Woodward LJ, Fergusson DM. Life course outcomes of young people with anxiety disorders in adolescence. J Am Acad Child Adolesc Psychiatry. 2001 Sep;40(9):1086-93. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Efficacy	Measures used to assess treatment efficacy: The Anxiety Disorders Interview Schedule for DSM-IV, Research and Lifetime Version for Children and Parents (Silverman & Albano, 1996); Multidimensional Anxiety Scale for Children (March et al., 1997); Youth Quality of Life Scale (Topolski et al., 2001),; Pediatric Anxiety Rating Scale (RUPP, 2002); Beck Depression Inventory-2 (Beck et al., 1996; Behavioral and Emotional Rating Scale-2 (Epstein & Sharma, 2004),; Clinical Global Impression Scale-Severity and Improvement (Guy, W. & ECDEU, 1976)	At week 16	No
Secondary	Physiological response to stress	Trier Social Stress Task for Children (TSST-C)[Baseline and week 18]; Salivary cortisol[For baseline, samples will be collected in the home upon awakening/8 am, +30, +60 min, at 4 pm, and at 8 pm on 2 consecutive weekdays. Cortisol will also be measured from samples collected before and after the TSST-C(-1, +10, +20, +30, +45, and +60 min)]; Salivary alpha-amylase[Before (-1), and +1, +10, +20, and +30 min after the TSST-C]; Heart rate variability[Baseline and during the TSST-C]; Acoustic Startle Response[Baseline and in a "fear-potentiated" condition with an ASR system]; Urine drug test	At week 18 - see below	No
Secondary	Suicide risk	At each treatment visit, the clinician will elicit AEs and SAEs, and complete the Columbia-Suicide Severity Rating Scale (C-SSRS) (Posner et al, 2007)	Each treatment visit (baseline then weeks 2, 4, 6, 8, 12, 16, 28)	Yes