Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia

NCT ID: NCT03772314

Last Updated: 2024-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-15
• Study Completion Date: 2023-05-04

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.

Conditions

Idiopathic Hypersomnia; Narcolepsy Without Cataplexy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Modafinil

Participants in this study arm will take modafinil.

Group Type: ACTIVE_COMPARATOR

Modafinil

Intervention Type: DRUG

Participants will received 100-400 milligrams (mg) per day of modafinil for 12 weeks.

Amphetamine-dextroamphetamine

Participants in this study arm will take amphetamine-dextroamphetamine (amphetamine salts).

Group Type: EXPERIMENTAL

Amphetamine-Dextroamphetamine

Intervention Type: DRUG

Participants will receive 10-40 mg/day of oral amphetamine salts for 12 weeks.

Interventions

Modafinil

Participants will received 100-400 milligrams (mg) per day of modafinil for 12 weeks.

Intervention Type: DRUG

Amphetamine-Dextroamphetamine

Participants will receive 10-40 mg/day of oral amphetamine salts for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Provigil; Adderall

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Academy of Sleep Medicine

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Lynn Marie Trotti

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lynn Marie Trotti, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory Sleep Center

Atlanta, Georgia, United States

Countries

United States

References

Trotti LM, Blake T, Hoque R, Rye DB, Sharma S, Bliwise DL. Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial. CNS Drugs. 2024 Nov;38(11):909-920. doi: 10.1007/s40263-024-01122-y. Epub 2024 Sep 21.

Reference Type: DERIVED

PMID: 39306601 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00108167

Identifier Type: -

Identifier Source: org_study_id