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. 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.
Full Title of Study: “Informing Treatment Decisions in the Central Disorders of Hypersomnolence: A Pragmatic Clinical Trial of Modafinil Versus Amphetamines”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Study Primary Completion Date: February 2022
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 sleep inertia, cognitive dysfunction, and sleepiness.
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 treatment-naïve 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.
- Drug: Modafinil
- Participants will received 100-400 milligrams (mg) per day of modafinil for 12 weeks.
- Drug: Amphetamine-Dextroamphetamine
- Participants will receive 10-40 mg/day of oral amphetamine salts for 12 weeks.
Arms, Groups and Cohorts
- Active Comparator: Modafinil
- Participants in this study arm will take modafinil.
- Experimental: Amphetamine-dextroamphetamine
- Participants in this study arm will take amphetamine-dextroamphetamine (amphetamine salts).
Clinical Trial Outcome Measures
- Change in Epworth Sleepiness Scale (ESS) Score
- Time Frame: Baseline, Week 12
- The Epworth Sleepiness Scale (ESS) asks respondents to indicate how likely they are to doze off or fall asleep during daytime situations such as reading or talking to someone. There are 8 items which are answered on a scale of 0 to 4 where 0 = would never doze and 4 = high chance of dozing. Total score can range from 0 to 24, with higher scores indicating more sleepiness. A score of 0 to 5 can be interpreted as “lower normal daytime sleepiness”, a score of 6 to 10 is “higher normal daytime sleepiness”, score between 11 to 12 are “mild excessive daytime sleepiness, scores of 13 to 15 are “moderate excessive daytime sleepiness” and scores of 16 to 24 indicate “severe excessive daytime sleepiness”.
- Change in Patient Global Impression of Change (PGIc) for Sleepiness Score
- Time Frame: Weeks 4, 8, 12
- The PGIc for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
- Change in Patient Global Impression of Change (PGIc) for Sleep Inertia Score
- Time Frame: Weeks 4, 8, 12
- The PGIc for Sleep Inertia asks respondents to rate their sleep interia compared to baseline. Sleep inertia is defined for participants as “difficulty waking up and getting out of bed in the morning because of sleepiness”. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
- Change in Patient Global Impression of Change (PGIc) for Cognitive Dysfunction Score
- Time Frame: Weeks 4, 8, 12
- The PGIc for Cognitive Dysfunction asks respondents to rate their cognitive dysfunction compared to baseline. Cognitive dysfunction is defined for participants as “difficulty with thinking, problems with attention or concentration, and/or brain fog”. Responses are indicated on a scale of 1 to 7 where 1 = very much improved and 7 = very much worse.
Participating in This Clinical Trial
- A diagnosis of idiopathic hypersomnia or narcolepsy type 2 (without cataplexy), according with the International Classification of Sleep Disorders, third edition (ICSD-3) criteria
- Obstructive sleep apnea (Apnea-Hypopnea Index (AHI) > 5)
- Severe periodic limb movements of sleep with arousals (periodic limb movements (PLM) arousal index > 30)
- Allergy to either of the study drugs
- Contraindication to either of the study drugs
- For modafinil, these contraindications include: history of left ventricular hypertrophy, mitral valve prolapse, severe cardiovascular disease, unstable angina, myocardial infarction, severe hepatic impairment, substance abuse history, psychosis, or unstable depression or mania
- Contraindications to amphetamine salts, in addition to those listed above, include: other cardiac structural abnormalities, cardiomyopathy, severe arrhythmias, uncontrolled hypertension, glaucoma, Tourette's syndrome, and epilepsy
- Women who are pregnant, planning to become pregnant within 16 weeks, or breastfeeding will be excluded
- Participants who have taken either modafinil or amphetamine salts for another indication will be excluded if it has been less than 12 months since this treatment
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Emory University
- American Academy of Sleep Medicine
- Provider of Information About this Clinical Study
- Principal Investigator: Lynn Marie Trotti, Associate Professor – Emory University
- Overall Official(s)
- Lynn Marie Trotti, MD, MSc, Principal Investigator, Emory University
- Overall Contact(s)
- Natalie Fernandez, 404-778-6114, firstname.lastname@example.org
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