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Completed

NCT Number: NCT03772314

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

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.

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Key information

Conditions

Idiopathic Hypersomnia Disorders of Excessive Somnolence Dyssomnias Mental Disorders Narcolepsy Without Cataplexy Nervous System Diseases Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Emory Sleep Center

Atlanta, Georgia, 30329, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Modafinil

Drug

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

Other names: Provigil

Amphetamine-Dextroamphetamine

Drug

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

Other names: Adderall

Primary outcomes

  1. 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". 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.

Secondary outcomes

  1. Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score

    Time frame: Week 12

    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.

  2. Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Overall Disease Severity Score

    Time frame: Week 12

    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.

  3. Number of Participants Reporting Any Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score

    Time frame: Week 12

    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.

  4. Number of Participants Reporting Much or Very Much Improvement From Baseline on Patient Global Impression of Change (PGIC) for Sleepiness Score

    Time frame: Week 12

    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.

  5. Number of Participants Reporting Any Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score

    Time frame: Week 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 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.

  6. Number of Participants Reporting Much or Very Much Improvement With Patient Global Impression of Change (PGIC) for Cognitive Dysfunction Score

    Time frame: Week 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", 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.

  7. Number of Participants Reporting Any Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score

    Time frame: Week 12

    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.

  8. Number of Participants Reporting Much or Very Much Improvement by Patient Global Impression of Change (PGIC) for Sleep Inertia Score

    Time frame: Week 12

    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.

  9. Change in Hypersomnia Severity Index (HSI) From Baseline

    Time frame: Baseline, Week 12

    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.

  10. Change in Sleep Inertia Questionnaire (SIQ) Score From Baseline

    Time frame: Baseline, Week 12

    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.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • American Academy of Sleep Medicine

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Dec 11, 2018
Registry last updated
May 23, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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