Use and safety of hydralazine in combination with valproate for the treatment of hypocretin deficiency in newly onset narcolepsy: A pilot study

ICTRP Trial ID
EUCTR2019-003671-19 (ICTRP)

Official title (approved by ethics committee)
Efficacy and safety of hydralazine in combination with valproate to treat hypocretin deficiency in recent onset narcolepsy: a pilot study (BASEC)

Academic title
Efficacy and safety of hydralazine in combination with valproate to treat hypocretin deficiency in recent onset narcolepsy: a pilot study - Hydralazine and valproate in recent onset narcolepsy (ICTRP)

Public title
Hydralazine and valproate in recent onset narcolepsy (ICTRP)

Disease under investigation
Narcolepsy type 1
MedDRA version: 20.0Level: PTClassification code 10028713Term: NarcolepsySystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)

Intervention under investigation

Trade Name: Hydralazine HCl CF
Pharmaceutical Form: Tablet
INN or Proposed INN: HYDRALAZINE HYDROCHLORIDE
CAS Number: 304-20-1
Other descriptive name: HYDRALAZINE HYDROCHLORIDE

Trade Name: Natriumvalproaat Chrono CF
Pharmaceutical Form: Tablet
INN or Proposed INN: SODIUM VALPROATE
CAS Number: 1069-66-5

(ICTRP)

Type of trial
Interventional clinical trial of medicinal product (ICTRP)

Trial design
Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no (ICTRP)

Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes

Inclusion criteria:
- Fulfilling the ICSD3 criteria for NT1, including a hypocretin-1 level in the CSF < 110 pg/ml.
- 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
(ICTRP)

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.


Primary and secondary end points
Primary end point(s): - Weekly cataplexy rate (complete/partial) as assessed in a diary before and after treatment.;Timepoint(s) of evaluation of this end point: Before and after administration of study medication.;Main Objective: To assess whether hydralazine in combination with valproate is effective in treating the symptoms of narcolepsy.;Secondary Objective: To assess the safety of treating NT1 patients with hydralazine in combination with valproate.
To assess whether the efficacy of hydralazine in combination with valproate is reflected in an increased concentration of hypocretin-1 in the CSF. (ICTRP)

Secondary end point(s): - Change in daytime sleepiness as assessed by the Epworth Sleepiness Scale (ESS).- Improvement of fragmentation index, sleep efficiency and REM latency on the polysomnography (PSG).
- Improvement of mean sleep latency (> 8 min) and/or sleep-onset REM periods (SOREMPs; < 2) during the Multiple Sleep Latency Test (MSLT);
- Adverse events (AEs);
- Changes in vital signs upon treatment;
- Increase in hypocretin-1 levels in the CSF measured by radioimmunoassay (only assessed if substantial improvement on the primary endpoints after 6 weeks of treatment, defined as ESS <12 or ESS > 4 points decreased and/or weekly cataplexy rate > 75% decreased).;Timepoint(s) of evaluation of this end point: Before and after administration of study medication. (ICTRP)

Registration date
13.01.2020 (ICTRP)

Incorporation of the first participant
13.01.2020 (ICTRP)

Secondary sponsors
not available

Additional contacts
Secretariaat Slaap-Waakcentrum, +310235588900, Stichting Epilepsie Instellingen Nederland (ICTRP)

Secondary trial IDs
71534 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003671-19 (ICTRP)