The Efficacy of Lower Dose Zolpidem for Achieving Satisfactory Sleep in Women With Disordered Sleep

Sleep difficulties are very common in adults in the U.S. today. Zolpidem (Ambien) is often prescribed as a first line agent to treat sleep difficulties in patients presenting with sleep related complaints to Primary Care Practitioners (PCP's). Zolpidem is currently available in two doses, 10 and 5 mg. These doses were developed in clinical studies carried out primarily on men. The first dose made clinically available, 10 mg, resulted in morbidity and mortality in many women because women metabolize Zolpidem at a slower rate than men, thus the half-life is longer. Women taking Zolpidem often had morning drowsiness, persistent sleepiness, and difficulty with tasks requiring coordination and judgement, such as motor vehicle operation. There were a number of well publicized motor vehicle crashes and fatalities attributed to Zolpidem, mostly among women. The company then produced a 5 mg dose; however, some women still reported side effects at the lower dose, suggesting persistent drug levels in the morning, when the drug purportedly should have been cleared from the body. These women would likely benefit from a lower dose, a dose personalized for their individual metabolisms and sleep difficulties. Lower doses of Zolpidem are only available from compounding pharmacies, which are not common, are expensive, do not take many insurances, and are not offered as an option to most patients. Vitae Industries, Inc. is a start-up tech company located in Providence, founded by a Brown University graduate, a chemical engineer, who has developed technology that can provide precisely varied amounts of drug for specific and variable personalized patient dosing. Personalized medicine is an area of great research and clinical interest to the medical community at large and the Brown University Medical School in particular. Brown also has a growing focus on issues of sex and gender in the rendering of clinical medical care. This technology has the potential to address both of these areas, providing the possibility of very specific, tailored drug dosing for men and women. This research was developed as a proof of concept study which will be carried out as a collaboration between Brown University Medical School/Lifespan physicians and the technical staff at Vitae Industries, Inc.. This work will be foundational and will serve as the medical and scientific justification for Vitae Industry's providing patient specific dosing of medications. For the purposes of this study, the medication to be tested, Zolpidem (Ambien) will be compounded by a licensed compounding Rhode Island pharmacy, PhusionRx, using standardized approaches to compounding and formulating pharmaceutical products. This study will use low doses of Zolpidem formulated by the licensed compounding pharmacy, PhusionRx. The investigators will provide graduated doses of Zolpidem to women participants meeting inclusion criteria who present to their primary care physician complaining of difficulty achieving satisfactory sleep. Participants will start at a dose of 0.5 mg of Zolpidem. Each day the quality of their sleep will be assessed by self-report. If they have not achieved satisfactory sleep at the starting dose of 0.5 mg, the will increase their dose daily by 0.5 mg until they reach the standard 5 mg dose or satisfactory sleep is achieved.

Study Overview

• Status: Unknown
• Conditions: Sleep Disorder
• Intervention / Treatment: Drug: Zolpidem

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Angela Jarman, MD MPH; Phone Number: 9196327961; Email: angela.jarman@gmail.com

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95819
      • Recruiting
      • Rhode Island Hospital
      • Contact: Angela Jarman; Phone Number: 919-632-7961; Email: angela.jarman@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Health Women with Disordered Sleep

Description

Inclusion Criteria:

• biologically female
• age 18-65
• English speaking
• difficulty sleeping

Exclusion Critieria:

• diagnosed significant cardiac, pulmonary, neuromuscular, hepatic, renal or major psychiatric disease (as ascertained by the study physicians)
• diagnosed sleep pathology such as sleep apnea or prior work-up for sleep pathology
• recent (two weeks prior) treatment of any kind for sleep disorder including herbal or over the counter treatments, psychiatric medications including anxiolytics except for SSRI's.
• pregnant or trying to become pregnant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; First 25 subjects	Drug: Zolpidem; PO sleep aid in various doses
2; Second cohort of 25 subjects	Drug: Zolpidem; PO sleep aid in various doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Quality	This will be based on the sleep journal	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects	Including daytime drowsiness, night walking/eating	7 days

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Collaborators: Vitae Industries, Inc
• Investigators: Principal Investigator: Bruce Becker, MD, Lifespan

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2019
• Primary Completion (Anticipated): July 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Sleep Wake Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; GABA Agents; Sleep Aids, Pharmaceutical; GABA-A Receptor Agonists; GABA Agonists; Zolpidem
• Other Study ID Numbers: Ambien Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No