Efficacy and safety of hydralazine in combination with valproate to treat hypocretin deficiency in recent onset narcolepsy: a pilot study

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 4

Inclusion Criteria

- Fulfilling the ICSD3 criteria for NT1, including a hypocretin-1 level in the
CSF < 110 pg/ml (sleep deprivation should be excluded).
- Recent symptoms of narcolepsy (<5 years).
- Baseline Epworth Sleepiness Scale (ESS) >= 14.
- > 7 cataplexy attacks per week (complete or partial) at baseline as assessed
by a cataplexy diary.
- Regular schedule for nocturnal sleep and time in bed > 6 hrs as assessed by
actigraphy and sleep diary.
- BMI 18-35 kg/m2.
- For females: use of a medically acceptable method of contraception for at
least 2 months prior to the first dose of study drug and consent to continue
the practice throughout the entire study and for 30 days after the study is
completed. No pregnancy planned for one year after participation.
- Willing and able to comply with the study design schedule and all other
requirements.
- Willing and able to provide written informed consent.

Exclusion Criteria

- Use of any psychotropic medication during the last 6 weeks before inclusion,
with exception for stimulants: use of stimulants during the last week before
inclusion.
- Pharmacological treatment for hypertension or epilepsy.
- Female subjects who are pregnant (as assessed by pregnancy test at baseline),
nursing or lactating.
- Occupation requiring nighttime shift work or variable shift work.
- Any other severe clinically relevant medical, behavioural, or psychiatric
disorder, particularly past or present condition of heart failure from aortic
stenosis and postural hypotension as diagnosed by a physician.
- Any contraindication against using either hydralazine or valproate.
- Significant laboratory abnormality as assessed during baseline.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Weekly cataplexy rate (complete/partial) as assessed in a diary before and<br /><br>after treatment.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Change in daytime sleepiness as assessed by the Epworth Sleepiness Scale<br /><br>(ESS).<br /><br>- Improvement of fragmentation index, sleep efficiency and REM latency on the<br /><br>polysomnography (PSG).<br /><br>- Improvement of mean sleep latency (> 8 min) and/or sleep-onset REM periods<br /><br>(SOREMPs; < 2) during the Multiple Sleep Latency Test (MSLT);<br /><br>- Adverse events (AEs);<br /><br>- Changes in blood pressure upon treatment;<br /><br>- Increase in hypocretin-1 levels in the CSF measured by radioimmunoassay (only<br /><br>assessed if substantial improvement on the primary endpoints after 6 weeks of<br /><br>treatment, defined as ESS <12 or ESS > 4 points decreased and/or weekly<br /><br>cataplexy rate > 75% decreased).</p><br>