Clinical trial NCT03772314: Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia
Official title: Informing Treatment Decisions in the Central Disorders of Hypersomnolence: A Pragmatic Clinical Trial of Modafinil Versus Amphetamines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Hypersomnia
Narcolepsy Without Cataplexy
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: American Academy of Sleep Medicine
First posted: 2018-12-11
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: For diseases that cause excessive daytime sleepiness (such as narcolepsy and idiopathic hypersomnia), there are several medications that can be used to treat sleepiness. However, it can be difficult to decide which medication to use for a particular individual for several reasons: 1) there are very few studies that directly compare two medications to see which works best; 2) there are very few studies that include people with a disorder of sleepiness called idiopathic hypersomnia.

To address this gap in knowledge, the researchers propose a randomized clinical trial comparing modafinil and amphetamine salts in patients with narcolepsy type 2 or idiopathic hypersomnia. All participants will either receive modafinil or amphetamine salts - no participant will receive placebo.

This study will evaluate which medication works better to improve sleepiness. The researchers will also see which medication is better for other symptoms including difficulty waking up and difficulty thinking, as well as seeing which medication causes fewer side effects. Finally, this study will see if any information about patients (such as age or sleep study features) predicts responding better to one medication or the other.

Detailed description: Currently, there are insufficient data to guide clinical practice regarding the use of amphetamines for the treatment of narcolepsy. This may be particularly important in the case of narcolepsy type 2, for which randomized, controlled trial data show that other treatments are less beneficial than they are for participants with narcolepsy type 1. For the closely related disorder of idiopathic hypersomnia, clinical trial data to guide treatment decision-making are even more limited, with only three published controlled trials ever performed.

To address these evidence gaps, the researchers propose a randomized, active-treatment controlled trial comparing modafinil and amphetamine salts for the treatment of narcolepsy type 2 and idiopathic hypersomnia. The primary outcome will be reduction in excessive daytime sleepiness, as measured by change in Epworth Sleepiness Scale scores from baseline to week 12 on treatment. Other important patient-reported outcomes will be considered as secondary outcomes, including Patient Global Impression of Change for overall severity, sleep inertia, cognitive dysfunction, and sleepiness, as well as other symptom questionnaires.

In addition to directly comparing the efficacy of these two medications for hypersomnolent patients, this study will also evaluate for relatively safety in this population. Further, this study will assess clinical predictors of treatment response. All three of these aims will be complementary in informing shared decision-making about whether to treat with modafinil or amphetamine salts.

Forty-four adult patients seeking evaluation at the Emory Sleep Center for narcolepsy type 2 or idiopathic hypersomnia will be invited to participate and will be randomized to one of the treatment arms upon consent. Participants will receive study treatment for 12 weeks. Participants complete questionnaires at baseline, week 4, week 8, and week 12, with week 12 as the pre-specified primary time point of assessment.

Eligibility criteria: Inclusion Criteria:

* narcolepsy type 2 or idiopathic hypersomnia
* ability to give informed consent

Exclusion Criteria:

* contraindication to modafinil or amphetamine salts (history of left ventricular hypertrophy, mitral valve prolapse, other cardiac structural abnormalities, severe cardiovascular disease, unstable angina, myocardial infarction, cardiomyopathy, severe arrhythmias, uncontrolled hypertension, severe hepatic impairment, substance abuse history, psychosis, glaucoma, Tourette's syndrome, and epilepsy)
* obstructive sleep apnea (Apnea-Hypopnea Index (AHI) \> 15)
* severe periodic limb movements of sleep with arousals (periodic limb movements (PLM) arousal index \> 30)
* allergy to either of the study drugs
* pregnancy or breastfeeding

Primary outcomes:
measure: Change in Epworth Sleepiness Scale (ESS) Score
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score
timeFrame: Week 12
measure: Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score
timeFrame: Week 12
measure: Number of Participants Reporting Any Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score
timeFrame: Week 12
measure: Number of Participants Reporting Much or Very Much Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score
timeFrame: Week 12
measure: Number of Participants Reporting Any Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score
timeFrame: Week 12
measure: Number of Participants Reporting Much or Very Much Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score
timeFrame: Week 12
measure: Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score
timeFrame: Week 12
measure: Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score
timeFrame: Week 12
measure: Change in Hypersomnia Severity Index (HSI) From Baseline
timeFrame: Baseline, Week 12
measure: Change in Sleep Inertia Questionnaire (SIQ) Score From Baseline
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Sleep Center
state: Georgia
Study officials:
affiliation: Emory University
name: Lynn Marie Trotti, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: