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

NCT02043977 | Completed Phase 1

• 1 other identifier: CL053
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Insomnia; Sleep Disorder; Dyssomnia

Keywords

Propofol; Insomnia; Sleep disorder; Sleep deprivation; Chronic insomnia; Refractory insomnia; Primary insomnia

Outcome Measures

Primary Outcomes (2)

• Mean change in the scores on the subjective assessment from the Leeds Sleep Evaluation Questionnaire

  180 days

• Mean change in the scores on the objective measurements of sleep architecture and patterns from polysomnography

  90 days

Secondary Outcomes (2)

• Changes in the scores on the SF(Short form)-35 quality of life questionnaire

  180 days

• 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

  5 days

Study Arms (1)

propofol infusion

EXPERIMENTAL

Induction of sleep is accomplished with a bolus of propofol (up to 0.5mg/kg over one minute, concurrently with a constant infusion of propofol starting at 25 ug/kg/min titrated to a maximum of 100ug/kg/min, to maintain the subject at a Modified Ramsay Score of 3-4 for a total of 120 minutes. An additional bolus may be given by the investigator in order to maintain the level of sleep. This procedure will be conducted over 5 consecutive nights.

Drug: propofol injectable emulsion

Interventions

propofol injectable emulsion DRUG

propofol infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Life Extension Foundation Inc.: lead

Study Sites (1)

Broward Health Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

Related 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.

  BACKGROUND

• 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. doi: 10.1097/00000542-200108000-00011.

  PMID: 11506101 BACKGROUND

• http://www.drugs.com/pro/propofol

  BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 11978233 BACKGROUND

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

  BACKGROUND

• 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. doi: 10.1093/sleep/34.3.283.

  PMID: 21358845 BACKGROUND

• Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002 Apr;6(2):97-111. doi: 10.1053/smrv.2002.0186.

  PMID: 12531146 BACKGROUND

• Rabelo FA, Braga A, Kupper 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.

  PMID: 20115978 BACKGROUND

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

  PMID: 10524487 BACKGROUND

• Ringdahl EN, Pereira SL, Delzell JE Jr. Treatment of primary insomnia. J Am Board Fam Pract. 2004 May-Jun;17(3):212-9. doi: 10.3122/jabfm.17.3.212.

  PMID: 15226287 BACKGROUND

• Roth T. Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007 Aug 15;3(5 Suppl):S7-10. No abstract available.

  PMID: 17824495 BACKGROUND

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

  PMID: 20814491 BACKGROUND

• 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. doi: 10.1097/00000542-200406000-00014.

  PMID: 15166561 BACKGROUND

• 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. doi: 10.1097/00000539-200105000-00028.

  PMID: 11323352 BACKGROUND

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

  PMID: 18175094 BACKGROUND

• 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.

  PMID: 21107748 BACKGROUND

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Dyssomnias; Sleep Deprivation

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Nervous System Diseases; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Edward A Czinn, M.D.

  Anesco North Broward LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 23, 2014
• Study Start: June 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: August 30, 2016

Record last verified: 2016-08

Locations

US (1)