The Effects of Modafinil to Counteract the Adverse Metabolic Consequences of Sleep Restriction

Sleep Restriction Clinical Trial

Official title:

Sleep Restriction, Impaired Glucose Metabolism, and Performance: The Effects of Modafinil to Counteract the Adverse Metabolic Consequences of Sleep Restriction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00895570
• Other study ID #: C1538/6032/ES/US
• Status: Completed
• Phase: N/A
• First received: May 6, 2009
• Last updated: May 7, 2009
• Start date: January 2005
• Est. completion date: April 2007

Study information

• Verified date: May 2009
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to examine the effects of sleep and modafinil on how the body processes glucose.

Description:

The occurrence and diagnosis of DM2 and its complications is increasing, leading to rising treatment costs that represent a considerable portion of the U.S. health care budget. Although treatment of impaired glucose tolerance (IGT) is not common, an IGT diagnosis increases the likelihood of progression to DM2. Careful attention to glycemic control is a primary treatment goal for DM2 patients, as glucose control reduces the severity of microvascular, macrovascular, and other complications.

Recent research has indicated that sleep loss could be a previously unrecognized risk factor for DM2. As sleep restriction has become an endemic condition in developed countries, it is possible that sleep loss contributes to the recent epidemic of DM2. Protecting sleep by increasing sleep duration and quality in DM2 and IGT patients may provide an inexpensive, relatively easy to implement intervention to reduce the risk of disease onset or delay disease progression by improving glucose tolerance. Furthermore, measurement of endocrine, metabolic, and cardiovascular parameters in the proposed studies may provide insights into the mechanisms by which sleep extension improves glucose tolerance under pathophysiological conditions.

The proposed study examines and quantifies in adults the link between insufficient sleep and increased insulin resistance, impaired insulin secretion, and reduced non-insulin-dependent glucose utilization by the sleepy brain. The proposed study capitalizes upon the unique pharmacological characteristics of modafinil to reverse excessive sleepiness to address the mechanisms by which sleep restriction may impact metabolism via excessive sleepiness. This study may lead to countermeasures to the adverse health impact of chronic insufficient sleep, an increasingly common lifestyle that may ultimately contribute to the development of the Metabolic Syndrome or DM2 via alterations of glucose metabolism and brain glucose utilization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• Subjects must have also demonstrated a full understanding of the requirements and demands of the study.

• Individuals must have been willing to follow a regular sleep-wake schedule.

Exclusion Criteria:

• Sleep/wake history. During completion of the preliminary telephone and written screening questionnaires, potential volunteers were asked a number of questions about their present, past and desired habitual sleep/wake schedule, including their habitual and desired bedtimes, wake-times, and nap times. Those potential volunteers with a history of night-work in the preceding 3-year period or travel across >2 time zones in the 3 months prior to the study were excluded.

• Individuals who are unable or unwilling to follow a regular sleep-wake schedule were excluded from the study.

• Drug/Alcohol Use. Volunteers must have been drug-free (including nicotine) and with moderate or no use of caffeine or alcohol for the entire duration of the study. No medications (prescription or over the counter) that significantly affect circadian rhythms, endocrine physiology, or sleep were allowed. They must have had no history of drug or alcohol dependency. No caffeine or alcohol were allowed for one week prior to or during the inpatient portion of the protocol. A comprehensive toxicological analysis of blood and urine for prescription medication, non-prescription medication, drugs of abuse, and caffeine, nicotine and alcohol metabolites was carried out for verification of reported non-use during the initial screening and on the day of admission to the laboratory for verification.

• Evaluation of Medical Suitability. Only healthy, non-obese men were selected for this study. Subjects must have been free from any acute, chronic or debilitating medical conditions. Normality was established on the basis of clinical history, electrocardiogram, clinical biochemical screening tests of blood and urine, and a physical examination conducted by a licensed physician. Any subject with symptoms of active illness (e.g., fever, leukocytosis, hypertension) was excluded from study. Given the wide range of illnesses that are encountered in medical practice, it would not be possible to provide a comprehensive list of each and every disease that could serve as grounds for exclusion for the subject. However, the following is a list of illnesses that would certainly have been grounds for exclusion: Chronobiologic Disorders, Sleep Disorders, Diseases of the Cardiovascular System, Disorders of the Kidney and Urinary Tract, Infectious Diseases, Disorders of the Gastrointestinal System, Disorders of the Immune System, Connective Tissue and Joints, Disorders of the Hematopoietic System, Neoplastic Diseases, Endocrine and Metabolic Diseases, Neurologic Disorders; significant impairments of the visual system.

• Evaluation of Psychiatric/Psychological Suitability. Each potential volunteer completed a series of psychological questionnaires received a comprehensive psychological examination by a clinical psychologist experienced with the psychological screening for the subjects in our studies. Individuals with evidence of psychopathology on standardized questionnaires or in a structured interview were excluded from study. Individuals with a history of psychiatric illnesses or psychiatric disorders were excluded. Individuals who are unaware of specific psychiatric diagnoses who have a history of having been treated with antidepressant, neuroleptic medications or major tranquilizers were excluded from study. However, a personal history of limited prior counseling or psychotherapy (e.g., for adjustment reactions) was not necessarily exclusionary. Potential subjects were evaluated for Axis II personality types that might interfere with protocol compliance or with their personal ability to tolerate the conditions of the study, such as temporal isolation and confinement.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Impaired Glucose Metabolism
• Sleep Restriction

Intervention

Drug:
• modafinil
During each day of the 7-day sleep restriction phase of the study modafinil was administered (200 mg tablet at 0600, and a second dose of 100 mg tablet at 1300).
• placebo
During each day of the 7-day sleep restriction phase of the study a sugar pill was administered.

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity measured with euglycemic hyperinsulinemic clamp		Following 3 nights of a continued 'sleep replete' period with 10 hours/night of time in bed and again following 7 days sleep restricted to 5 hrs time in bed/night	No
Secondary	Insulin release (i.e., pancreatic beta cell function) measured on IVGTT		Following 3 nights of a continued 'sleep replete' period with 10 hours/night of time in bed and again following 7 days sleep restricted to 5 hrs time in bed/night	No
Secondary	Glucose effectiveness measured using an IVGTT, clamp		Following 3 nights of a continued 'sleep replete' period with 10 hours/night of time in bed and again following 7 days sleep restricted to 5 hrs time in bed/night	No
Secondary	Biomarkers of Sleep Loss (HbA1c, fructosamine, insulin, glucose, cortisol thyrotropic axis function, lipid metabolism, leptin, ghrelin and cytokine signaling)		Following 3 nights of a continued 'sleep replete' period with 10 hours/night of time in bed and again following 7 days sleep restricted to 5 hrs time in bed/night	No
Secondary	Subjective measures of sleepiness and alertness		Every 3 hours while awake during the 12-day inpatient stay	No
Secondary	RMR assessed by indirect calorimetry		On the morning and late afternoon of day 4 and 11	No
Secondary	Urinary catecholamines levels		Over 24 hours on days 3, 4, 10, 11	No
Secondary	Salivary free cortisol		Every 30 minutes in the afternoon of days 3, 4, 10, 11	No
Secondary	Neurobehavioral performance		approx very 3 hours during wake in the 12-day inpatient stay	No