Efficacy and Safety Study of Propofol Infusion for Refractory Chronic Primary Insomnia

Insomnia Clinical Trial

Official title:

An Open Label, Pilot Study Utilizing an IV Infusion of Propofol in Male and Female Volunteers With Refractory Chronic Primary Insomnia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02043977
• Other study ID #: CL053
• Status: Completed
• Phase: Phase 1
• First received: January 14, 2014
• Last updated: August 26, 2016
• Start date: June 2013
• Est. completion date: May 2015

Study information

• Verified date: August 2016
• Source: Life Extension Foundation Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Insomnia is a widespread condition in which approximately one-third of adults in the United States are symptomatic with 6% of the population meeting the diagnostic criteria for insomnia. There is an increased risk of insomnia in certain segments of the population including women, middle-aged and older adults, shift workers and individuals with medical or psychiatric disorders. Individuals with insomnia have a decreased quality of life compared to those who report other serious illnesses such as major depression and congestive heart failure. Chronic insomnia can be caused by medications, drug or alcohol abuse, psychiatric disorders, medical and neurologic disorders. It can impair cognitive and physical functioning.

Propofol is an approved drug administered intravenously for use in the induction and maintenance of anesthesia or sedation. Some research suggests that propofol when administered as a two hour infusion may improve the ease of sleep onset, sleep quality, ease of awakening and the integrity of behavior following waking.

This study will be conducted in the Broward Health Medical Center Sleep Lab, under the direct care of a Board Certified Anesthesiologist, dedicated to the study involving participants who have refractory chronic primary insomnia and have not responded to conventional pharmacologic therapies within the past 90 days. Each qualifying participant will receive an IV infusion of the study medication for 5 consecutive nights. Assessments including polysomnography with completion of questionnaires will occur at screening, Days 1 through 5 of study product administration, Day 6 and Day 90. Follow-up questionnaires will also be distributed on Day 180.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Ambulatory, male or non-pregnant, non-lactating female, 18-65 years of age.

• Overall healthy with no other sleep disorder such as sleep apnea or periodic limb movement disorder

• Has not responded to conventional pharmacologic therapies (benzodiazepines and non-benzodiazepines) within the past 90 days. The non-benzodiazepine therapies can include melatonin and melatonin receptor agonists, antihistamines, antidepressants, over-the-counter medications, supplements or herbs for sleep

• Have refractory chronic primary insomnia (chronic-inadequate quantity or quality of sleep characterized by a subjective report of difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity for sleep, and results in some form of daytime impairment and has persisted for at least one month., primary-insomnia independent of any known physical or mental condition, refractory-not yielding, at least not yielding readily to treatment based upon polysomnography at baseline, total sleep time (sTST) of < 6 hr, a subjective wake time after sleep onset (WASO) of >1 hr, a subjective latency to sleep onset (SOL) of > 20 min

• Willing and able to give written informed consent

• Clearly understands the procedures and requirements for the study

• Willing and able to comply with all study procedures and data recording obligations for the entire length of the study

• Have no clinically significant abnormalities on the basis of medical history, physical examination and vital signs in the judgment of the investigator and/or sub-investigator

• Ability and willingness to abstain from any pharmaceutical or over-the-counter medication for sleep as well as alcohol from 72 hours prior to baseline and the first dose until after completion of the Study Product Administration Follow-Up Visit (Day 6) as well as 72 hours prior to the Day 90 visit.

• All values for hematology and for clinical chemistry tests of blood within the normal range for age and gender or showing no clinically relevant deviations as judged by the investigator

• Nonsmoking or have quit smoking at least 6 months prior to dosing

Exclusion Criteria:

• Having any medical conditions including diabetes, cardiovascular disease, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric (including depression), immunologic, hematologic, gastrointestinal or metabolic disease requiring medical treatment that would preclude participation into the study in the judgment of the investigator/sub-investigator

• Having ingested any pharmaceutical or over-the-counter sleep product within 72 hours of dosing as well as 72 hours prior to the Day 90 visit.

• Taking any medication that can yield a moderate to major drug interaction with propofol including those with CNS (central nervous system)-depressant effects

• Having had a history of any medical or surgical procedure that would preclude participation into the study in the judgment of the investigator/sub-investigator

• Being pregnant, planning on becoming pregnant, breast feeding or unwilling to use a medically acceptable form of birth control during the study (with at least one acceptable barrier for a period of one month prior to the beginning of the study until at least three months after study completion) or are surgically sterile or postmenopausal (at least 12 months without a period).

• Having a systolic blood pressure >160 mmHg, diastolic blood pressure >90 mmHg, or blood pressure that would preclude participation in the judgment of the investigator/sub-investigator

• Having a previous history of abnormal screening laboratory test values: bilirubin > 2 x ULN (upper limit of normal), AST(aspartate aminotransferase) and ALT (alanine aminotransferase) > 2 x ULN (upper limit of normal), serum creatinine > 1.5 mg/dl, fasting blood glucose below 85mg/dl or above 110 mg/dl, calcium level < 8.6 mg/dl and triglycerides >200.0mg/dl.

• Any type of active malignancy (except non-melanomatous skin malignancies) within the past 5 years

• History of known or suspected substance abuse

• Currently consume more than 7 standard alcoholic drinks per week and unable to refrain from consuming an alcoholic beverage during the course of the study dosing period.

• Currently consume more than 14 caffeinated beverages per week and unable to refrain from consuming a caffeinated beverage within 8 hours prior to dosing.

• History of allergy to any anesthetic, eggs, egg products, soybeans or soy products as well as hypersensitivity to Propofol or any of its components

• Unable to avoid engaging in a hazardous occupation requiring complete mental alertness and/or motor coordination after receiving the study product.

• Participation in another study within 30 days prior to dosing.

• Donated blood within 30 days prior to dosing.

• Illness within five days prior to dosing

• Having a pacemaker or any internal medical device

• In the opinion of the investigator, not suitable for entry into the study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Dyssomnia
• Dyssomnias
• Insomnia
• Parasomnias
• Sleep Disorder
• Sleep Initiation and Maintenance Disorders
• Sleep Wake Disorders

Intervention

Drug:
• propofol injectable emulsion

Locations

Country	Name	City	State
United States	Broward Health Medical Center	Fort Lauderdale	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Life Extension Foundation Inc.

Country where clinical trial is conducted

United States, 

References & Publications (17)

American College of Chest Physicians. Diagnosis and Treatment of Insomnia. http://chestnet.org/accp/pccsu/diagnosis-and-treatment-insomnia?page=0.3. Published September 3, 2007. Accessed February 6, 2012.

Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, Gambus PL, Shafer SL. Propofol dosing regimens for ICU sedation based upon an integrated pharmacokinetic-pharmacodynamic model. Anesthesiology. 2001 Aug;95(2):324-33. — View Citation

http://www.drugs.com/mmx/propofol.html)

http://www.drugs.com/pro/propofol

Katz DA, McHorney CA. The relationship between insomnia and health-related quality of life in patients with chronic illness. J Fam Pract. 2002 Mar;51(3):229-35. — View Citation

Mace AE. Sample-Size Determination. New York: Reinhold Publishing Corporation, 1964.

Murphy M, Bruno MA, Riedner BA, Boveroux P, Noirhomme Q, Landsness EC, Brichant JF, Phillips C, Massimini M, Laureys S, Tononi G, Boly M. Propofol anesthesia and sleep: a high-density EEG study. Sleep. 2011 Mar 1;34(3):283-91A. — View Citation

Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002 Apr;6(2):97-111. — View Citation

Rabelo FA, Braga A, Küpper DS, De Oliveira JA, Lopes FM, de Lima Mattos PL, Barreto SG, Sander HH, Fernandes RM, Valera FC. Propofol-induced sleep: polysomnographic evaluation of patients with obstructive sleep apnea and controls. Otolaryngol Head Neck Surg. 2010 Feb;142(2):218-24. doi: 10.1016/j.otohns.2009.11.002. — View Citation

Rajput V, Bromley SM. Chronic insomnia: a practical review. Am Fam Physician. 1999 Oct 1;60(5):1431-8; discussion 1441-2. — View Citation

Ringdahl EN, Pereira SL, Delzell JE Jr. Treatment of primary insomnia. J Am Board Fam Pract. 2004 May-Jun;17(3):212-9. Review. — View Citation

Roth T. Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007 Aug 15;3(5 Suppl):S7-10. Review. — View Citation

Saddichha S. Diagnosis and treatment of chronic insomnia. Ann Indian Acad Neurol. 2010 Apr;13(2):94-102. doi: 10.4103/0972-2327.64628. — View Citation

Tung A, Bergmann BM, Herrera S, Cao D, Mendelson WB. Recovery from sleep deprivation occurs during propofol anesthesia. Anesthesiology. 2004 Jun;100(6):1419-26. — View Citation

Tung A, Lynch JP, Mendelson WB. Prolonged sedation with propofol in the rat does not result in sleep deprivation. Anesth Analg. 2001 May;92(5):1232-6. — View Citation

Vanlersberghe C, Camu F. Propofol. Handb Exp Pharmacol. 2008;(182):227-52. doi: 10.1007/978-3-540-74806-9_11. Review. — View Citation

Xu Z, Jiang X, Li W, Gao D, Li X, Liu J. Propofol-induced sleep: efficacy and safety in patients with refractory chronic primary insomnia. Cell Biochem Biophys. 2011 Jul;60(3):161-6. doi: 10.1007/s12013-010-9135-7. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in the scores on the subjective assessment from the Leeds Sleep Evaluation Questionnaire		180 days	No
Primary	Mean change in the scores on the objective measurements of sleep architecture and patterns from polysomnography		90 days	No
Secondary	Changes in the scores on the SF(Short form)-35 quality of life questionnaire		180 days	No
Secondary	Changes in safety parameters from the propofol infusion compared to baseline measured by laboratory markers, vital signs, electrocardiogram, pulse oximeter, physical exam and any adverse events	Laboratory markers including complete blood count/chemistry values. Vital signs including blood pressure, pulse and temperature.	5 days	Yes