Effects of Temazepam in Patients With Chronic Pulmonary Obstructive Disease

Condition(s) targeted: Chronic Obstructive Pulmonary Disease

Intervention: Temazepam (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Rijnstate Hospital

Official(s) and/or principal investigator(s):
Gerben Stege, MD, Principal Investigator, Affiliation: Rijnstate Hospital
Peter J de Bruijn, MD, Study Director, Affiliation: Rijnstate Hospital
Richard PN Dekhuijzen, Prof. PhD MD, Study Director, Affiliation: UMC St. Radboud
Frank JJ van den Elshout, PhD MD, Study Director, Affiliation: Rijnstate Hospital
Yvonne F Heijdra, PhD MD, Study Director, Affiliation: UMC St. Radboud
Marjo JT van de Ven, PhD MD, Study Director, Affiliation: Rijnstate Hospital
Petra JE Vos, PhD MD, Study Chair, Affiliation: Rijnstate Hospital

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.

Official title: Effects of Temazepam on Dyspnea, Gas Exchange and Sleep Quality in Chronic Obstructive Pulmonary Disease.

Study design: Treatment, Randomized, Double-Blind, Crossover Assignment, Safety/Efficacy Study

Primary outcome:

transcutaneous PCO2

transcutaneous PO2

Oxygen saturation

Secondary outcome:

Respiratory Disturbance Index

Desaturation Index

MSLT

arterial PO2

arterial PCO2

Hypercapnic Ventilatory Response

total sleeping time

sleep latency

percentage REM- and nREM-sleep of total sleep time

number of arousals

number of apneas during sleep

number of hypopneas during sleep

Epworth Sleeping Score

Dyspnea Visual Analog Score

Detailed 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Rijnstate Hospital, Arnhem, Gelderland 6800 TA, Netherlands

sponsor's web site

Starting date: October 2005
Ending date: August 2007
Last updated: October 31, 2007