Effects of Temazepam in Patients With Chronic Pulmonary Obstructive Disease

Rijnstate Hospital

Status and phase

Completed

Phase 3

Conditions

Chronic Obstructive Pulmonary Disease

Treatments

Drug: Temazepam

Study type

Interventional

Funder types

Other

Identifiers

NCT00245661

LTC-346/050905/Stege

Details and patient eligibility

About

The purpose of this study is to evaluate the effects of temazepam during sleep and in daytime on dyspnea, gas exchange and sleep quality in patients with chronic obstructive pulmonary disease.

The study hypothesis is that temazepam does not produce any adverse respiratory effects during sleep in patients with COPD. In contrast, it may result in an beneficiary effect because it positively affects the sleep quality and sleep structure which may result in more alertness and less daytime sleepiness and less dyspnea during the day.

Full description

Rationale: More than 50% of patients with chronic obstructive pulmonary disease (COPD) have sleep complaints characterised by longer latency to falling asleep, more frequent arousals and awakenings, generalised insomnia and/or excessive daytime sleepiness. Sleep disturbance seems to be more severe with advancing disease and substantially reduces patients' quality of life. The sleep complaints are due to dyspnea, chronic cough, sputum production, hypoxaemia and hypercapnia during the night. One of the available therapies for these patients is the prescription of hypnotics (like benzodiazepines). However, it is thought that in patients with COPD sleep medication may produce adverse respiratory effects due to suppression of the cerebral respiratory drive. In our practice, we never encounter any adverse respiratory effect of an hypnotic in patients with COPD. There have been several trials in COPD patients studying these potentially adverse effects. The results of these studies are inconsistent, relative older hypnotics are used and there are several methodological limitations. Furthermore, in none of these studies transcutaneous PCO2 or PO2 was monitored. Temazepam is nowadays the sedative of first choice in the medical treatment of sleep complaints.

Aim: primary: studying the effects of temazepam on the respiratory function during daytime and at night in patients with severe COPD. Secondary: studying the effects of temazepam on the sleep quality and sleep structure and on the objective and subjective sleepiness during daytime and at night in patients with COPD.

Study design: double blind, placebo-controlled, cross-over randomised clinical trial.

Treatment: 10 mg temazepam or placebo during seven consecutive nights.

Endpoints: Primary: difference in PtcCO2, PtcO2 and oxygen saturation during sleep after 1 week temazepam compared to placebo. Secondary: Respiratory Disturbance Index, Desaturation Index and Hypercapnic Ventilatory Response, percentage REM/nREM-sleep and total effective sleep time, Multiple Sleep Latency Test and the Epworth Sleeping Score.

Enrollment

14 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

diagnosis of COPD, GOLD 3 or 4
having subjective sleeping problems
- longer latency to falling asleep
- frequent arousals
- excessive daytime sleepiness
clinical stable health for minimally 6 weeks

Exclusion criteria

usage of some sort of medication that influences sleep in any kind of way (like benzodiazepines, barbiturates, opiates, amfetamines) which can not be discontinued during the study period
alcohol abuse
hospitalisation 6 weeks or shorter before enrollment in the study
hyperreactivity / allergy to benzodiazepines
history of benzodiazepine-dependence
myasthenia gravis
obstructive sleep apnea syndrome (OSAS)
severe liver failure
age under 18 years
participation in another study less than 6 weeks before enrollment
COPD exacerbation less than 6 weeks before enrollment
usage of oxygen supplementation at home