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

Idiopathic Hypersomnia Clinical Trial

Official title:

Informing Treatment Decisions in the Central Disorders of Hypersomnolence: A Pragmatic Clinical Trial of Modafinil Versus Amphetamines

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03772314
• Other study ID #: IRB00108167
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2019
• Est. completion date: May 4, 2023

Study information

• Verified date: April 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: May 4, 2023
• Est. primary completion date: May 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cataplexy
• Disorders of Excessive Somnolence
• Idiopathic Hypersomnia
• Narcolepsy
• Narcolepsy Without Cataplexy

Intervention

Drug:
• Modafinil
Participants will received 100-400 milligrams (mg) per day of modafinil for 12 weeks.
• Amphetamine-Dextroamphetamine
Participants will receive 10-40 mg/day of oral amphetamine salts for 12 weeks.

Locations

Country	Name	City	State
United States	Emory Sleep Center	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	American Academy of Sleep Medicine Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Epworth Sleepiness Scale (ESS) Score	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". The change in ESS score is obtained by subtracting the total score at week 12 from the baseline score. Scores above 0 mean that the mean score at Week 12 was lower than the mean score at Baseline, indicating less sleepiness.	Baseline, Week 12
Secondary	Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score	The PGIC for Overall Severity asks respondents to rate their overall disease compared to baseline. Responses are indicated on a 7-point scale where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved", or "very much improved") and treatment non-responders (responses of "no change" to "very much worse"). The number of participants reporting any improvement at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score	The PGIC for Overall Severity asks respondents to rate their overall disease compared to baseline. Responses are indicated on a scale of 1 to 7 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Any Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score	The PGIC for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a 7-point scale where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved", or "very much improved") and treatment non-responders (responses of "no change" to "very much worse"). The number of participants reporting any improvement at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Much or Very Much Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score	The PGIC for Sleepiness asks respondents to rate their sleepiness compared to baseline. Responses are indicated on a 7-point scale where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Any Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score	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 where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved", or "very much improved") and treatment non-responders (responses of "no change" to "very much worse"). The number of participants reporting any improvement at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Much or Very Much Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score	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", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score	The PGIC for Sleep Inertia asks respondents to rate their sleep inertia 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", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". Responses were dichotomized into groups of participants who were treatment responders having any level of improvement (responses of "minimally improved", "much improved", or "very much improved") and treatment non-responders (responses of "no change" to "very much worse"). The number of participants reporting any improvement at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score	The PGIC for Sleep Inertia asks respondents to rate their sleep inertia 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", 2 = "much improved", 3 = "minimally improved" 4 = "no change", 5 = "minimally worse", 6 = "much worse" and 7 = "very much worse". The number of participants reporting "much improved" or "very much improved" at the Week 12 assessment compared to how they felt right before starting the study medication was examined.	Week 12
Secondary	Change in Hypersomnia Severity Index (HSI) From Baseline	The HSI is a 9-item instrument assessing the severity of excessive sleepiness (hypersomnolence). Items are scored on a Likert scale where 0 = not at all and 4 = very much. Total scores range from 0 to 36 and higher scores indicate greater severity of symptoms of hypersomnia. The change in HSI score is obtained by subtracting the total score at week 12 from the baseline score. Scores above 0 signify that the mean score at Week 12 was lower than the mean score at Baseline, indicating reduced severity of hypersomnia symptoms.	Baseline, Week 12
Secondary	Change in Sleep Inertia Questionnaire (SIQ) Score From Baseline	The SIQ is an instrument with 21 items with responses on a 5-point scale where 1 = "not at all" and 5 = "all the time". Two additional questions relate to how much time it takes for the respondent to wake up in the morning. For these analyses, a total score for the 21 items was generated. The change in SIQ score is obtained by subtracting the total score at week 12 from the baseline score. Scores above 0 signify that the mean score at Week 12 was lower than the mean score at Baseline, indicating reduced difficulty awakening.	Baseline, Week 12