Clinical trial NCT03785223: A 14 Week, Randomized, Placebo-Controlled Cross-Over Study of Methylphenidate Hydrochloride Controlled Release Capsules in Adult ADHD With and Without Anxiety Disorder Comorbidity
Official title: A 14 Week, Randomized, Placebo-Controlled Cross-Over Study of Methylphenidate Hydrochloride Controlled Release Capsules in Adult ADHD With and Without Anxiety Disorder Comorbidity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder
Generalized Anxiety Disorder
Social Anxiety Disorder
Panic Disorder
Agoraphobia
Keywords: ADHD
Anxiety Disorders
Stimulants
Methylphenidate
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Purdue Pharma, Canada
First posted: 2018-12-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Other psychiatric disorders, including anxiety, often co-occur with adult ADHD; with 85% of ADHD patients having at least one other psychiatric condition. The presence of a co-occurring anxiety disorder has been associated with additive clinical effects, leading to more global impairment, poorer outcome, greater resistance to treatment and increased costs of illness. Stimulants are effective first-line treatments for adult ADHD patients, however the literature has mostly examined these treatments in pure ADHD populations (i.e. without other psychiatric disorders). Thus, there is little information to guide physicians in making treatment decisions for patients with ADHD and a co-occurring condition.

This trial aims to evaluate the efficacy and safety of methylphenidate hydrochloride controlled release capsules (Foquest) in treating adults aged 18-65 years with DSM-5 ADHD with and without a co-occurring anxiety disorder.The study uses a 14-week, randomized, placebo-controlled, cross-over design.


Eligibility criteria: Inclusion Criteria:

1. Outpatient men and women between 18 and 65 years who meet criteria for Current DSM-5 ADHDalone or with one of the following DSM-5 diagnoses: GAD, SAD,PD or Agoraphobia. Major Depressive Disorder or Persistent Depressive Disorder will be allowed, providing the severity is considered moderate or less, as defined by a score on the Montgomery Depressive Rating Scale-MADRS score of ≤ 25.
2. ADHD rating scale for DSM-5 (ADHD-5-RS) score ≥ 24.
3. Concomitant treatment with selective serotonin reuptake inhibitors (SSRI's), serotonin noradrenaline reuptake inhibitors (SNRI's), benzodiazepines, beta-blockers, atypical anti-psychotics, anti-epileptics is allowed, provided the dose has been stable for 8 weeks prior to study entry. Dose changes of allowed concomitant medication should be avoided during the treatment phases of the study.
4. The ability to comprehend and satisfactorily comply with protocol requirements.
5. Written informed consent given prior to entering the baseline period of the study.
6. All women of child bearing potential must have a negative screening visit serum or urine pregnancy test and be using adequate contraception for the duration of the study. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices or properly used barrier contraception. Additionally, the use of condoms is suggested as an adjunct to the methods previously addressed to provide additional protection against accidental pregnancy.

Exclusion Criteria:

1. Participants who currently fulfill criteria for a lifetime history of bipolar disorder, schizophrenia or other psychotic disorders, delirium, dementia and amnesic and other cognitive disorders, severe head injury, autism spectrum disorders, or are in a current agitated state.
2. Participants with a history of seizure disorders, or an unstable medical condition will also be excluded.
3. Participants with significant suicidal ideation (MADRS item 10 score \> 3) or who have enacted suicidal behaviours within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
4. Current treatment with a stimulant.
5. A history of \> 2 failed trials of adequately dosed psychostimulants for Adult ADHD.
6. Patients receiving current psychotherapy, including cognitive behavioural therapy for either ADHD or an anxiety disorder, within 4 weeks prior to the baseline period.
7. Patients who are known to be allergic to methylphenidate or components of methylphenidate hydrochloride, have known hypersensitivity or idiosyncrasy to methylphenidate hydrochloride.
8. Patients who have thyroid pathology, treatment of which has not been stabilized for at least 3 months.
9. MAO inhibitors within 3 weeks of the start of the baseline.
10. Individuals meeting criteria for current cannabis use disorder or substance use disorder will be excluded.
11. Current use of bupropion or tri-cyclic antidepressants, with the exception of clomipramine.
12. Current use of clonidine, modafinil or atomoxetine.
13. Previous intolerance or failure to respond to an adequate trial of methylphenidate hydrochloride controlled release capsules (defined as a minimum of 55mg per day for at least 4 weeks).
14. Patients who have a history or evidence of a medical condition that would expose them to an increase or significant adverse event or interfere with assessments of safety and efficacy during the course of the trial including: advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, or other pre-existing cardiac abnormalities or other serious cardiac problems.
15. Patients with a history of Glaucoma.
16. Sleep medications during the study period are excluded with the exception of zopiclone and zolpidem and melatonin.
17. Patients using any herbal psychoactive treatments, eg; St.John's Wort, Valerian, Kava Kava, or Chamomile Extract within 14 days prior to randomization.
18. Patients who have received electroconvulsive therapy within the previous 6 months.
19. Patients with any condition or on any therapy that in the investigator's opinion or as indicated in the methylphenidate hydrochlorideproduct label, that may pose a risk to the subject or interfere with the study objective.
20. Patients having clinically significant abnormal laboratory or ECG findings not resolved by the baseline examination.
21. Patients with a proximal family history of sudden, unexplained cardiac death.

Primary outcomes:
measure: Attention Deficit and Hyperactivity Rating Scale - 5
timeFrame: Change from baseline to Week 12
Secondary outcomes:
measure: Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: Change from baseline to Week 12
measure: Clinical Global Impression - Severity (CGI-S)
timeFrame: Change from baseline to Week 12
measure: Clinical Global Impression - Improvement (CGI-I)
timeFrame: Change from baseline to Week 12
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline to Week 12
measure: Barkley Adult ADHD Rating Scale (BAARS-IV)
timeFrame: Change from baseline to Week 12
measure: Weiss Functional Impairment Rating Scale-Self Report (WFIRS-S)
timeFrame: Change from baseline to Week 12
measure: Barkley Deficits in Executive Functioning Scale (BDEFS)
timeFrame: Change from baseline to Week 12
measure: Overall Anxiety Severity and Impairment Scale (OASIS)
timeFrame: Change from baseline to Week 12
measure: Obsessive Compulsive Inventory - Revised (OCI-R)
timeFrame: Change from baseline to Week 12
measure: Quick Inventory of Depressive Symptoms (QID-SR-16)
timeFrame: Change from baseline to Week 12
measure: Sheehan Disability Scale (SDS)
timeFrame: Change from baseline to Week 12
measure: Social Phobia Inventory (SPIN)
timeFrame: Change from baseline to Week 12
measure: Generalized Anxiety Disorder-7
timeFrame: Change from baseline to Week 12
measure: Panic and Agoraphobia Scale (PAS)
timeFrame: Change from baseline to Week 12
measure: PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Change from baseline to Week 12
measure: Drug Abuse Screening Test (DAST)
timeFrame: Change from baseline to Week 12
measure: Alcohol Use Disorders Identification Test (AUDIT)
timeFrame: Change from baseline to Week 12
measure: Cannabis Use Disorder Identification Test-Revised (CUDIT-R)
timeFrame: Change from baseline to Week 12
measure: Hoarding Rating Scale (HRS)
timeFrame: Change from baseline to Week 12
measure: Binge Eating Scale (BES)
timeFrame: Change from baseline to Week 12
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Change from baseline to Week 12
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: MacAnxiety Research Center
state: Ontario
Study officials:
affiliation: McMaster University
name: Michael Van Ameringen, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: