Insomnia
Conditions
Keywords
insomnia, inflammation, stress
Brief summary
The main purpose of this study is to understand how insomnia (compared to good sleep) may affect the response of the body to a repeated physiological challenge, such as inserting the hand in ice-cold water for several times in a row. In particular, the investigators are interested in the response of markers that can be associated with stress, such as blood pressure and stress hormones.
Detailed description
Sleep is critical for the regulation and maintenance of biological systems, and sleep deficiency, such as insomnia, has been shown to be associated with elevated risks for cardiovascular, metabolic, and mood disorders. Despite the high prevalence of insomnia in the population, the investigators understanding of the biological consequences of the disorder with respect to inflammatory, autonomic, and stress system markers is limited, and often not consistent. In addition, insomnia may not only alter the basal activity of these systems, but may change their reactivity to other stressors and challenges. In support of this assumption are findings showing that poor sleep quality in healthy individuals is associated with a stronger biological response to a stressful challenge, such as the cold pressor test. This test involves the immersion of the hand in ice-cold water. It is one of the most commonly used laboratory physiological challenge tests, provoking not only unpleasantness, but also increases in stress and inflammatory markers. Investigations of such system's reactivity to challenge may elucidate systems abnormalities that the investigators do not capture by only assessing basal system's levels. For example, in patients with rheumatoid arthritis, basal inflammatory levels are normal, but the response to a physiological stress challenge (cold pressor test) is amplified. To the investigators knowledge, no studies have measured how insomnia may affect the reactivity of biological systems to a stressful challenge, which may serve as an important indicator of system's dysregulation and associated disease risk. In this light, the primary goal of this proposal will investigate whether stress-related systems are more reactive to a physiological stressful challenge in insomnia disorder compared to healthy controls.
Interventions
BEHAVIORALCold Pressor Test
Repeated immersion of hand in ice-cold water
Sponsors
Beth Israel Deaconess Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Women and men between the ages 18-55 years * Blood chemistry in the normal range * BMI less than or equal to 35 Specific to insomnia group: * Diagnosis of insomnia disorder based on DSM-V criteria Specific for control group: * Good quality and quantity sleep
Exclusion criteria
* Active infection/disease. * History of neurological, chronic pain, immune, cardiovascular, liver/kidney, or metabolic disorder * History of psychiatric disorders within the last 6 months prior to study start * Sleep disorders other than insomnia * Reynaud's disease * Psychotropic, sleep, or any other medications or herbs interfering with the inflammatory, autonomic, or HPA system in the last 2 weeks prior to study start, except oral contraceptives * In psychotherapy or any other behavioral interventions at study start * Donation of blood or platelets within 3 months of hospital visits * Pregnant/nursing. * Substance abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT. | Inflammatory marker: Change in plasma levels of IL-6 (pg/mL). |
| Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT. | HPA marker: Change in serum cortisol levels (ug/dL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes | Monocytes are only obtained from the baseline blood draw, which occurs at 11am. | Percentage of IL-6 positive monocytes following stimulation with LPS (100pg/mL) and varying concentrations of Dexamethasone |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen. | 22 |
| Insomnia Disorder Participants with the diagnosis of insomnia disorder (according to DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen. | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Healthy Controls | Insomnia Disorder | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 22 Participants | 44 Participants |
| Age, Continuous | 26.09 years | 30.27 years | 28.18 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 12 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 11 Participants | 16 Participants | 27 Participants |
| Region of Enrollment United States | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 37 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6
Inflammatory marker: Change in plasma levels of IL-6 (pg/mL).
Time frame: Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.
Population: Data of 3 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 50 min after CPT 1 | 3.0318 pg/mL | Standard Error 0.55967 |
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 50 min after CPT 2 | 4.2044 pg/mL | Standard Error 0.64394 |
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 20min after CPT 1 | 2.5911 pg/mL | Standard Error 0.49528 |
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 20 min after CPT 3 | 5.514 pg/mL | Standard Error 0.82173 |
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 20 min after CPT 2 | 3.7131 pg/mL | Standard Error 0.65019 |
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 50 min after CPT 3 | 5.9841 pg/mL | Standard Error 1.15086 |
| Healthy Controls | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | Baseline | 1.5013 pg/mL | Standard Error 0.16892 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 50 min after CPT 3 | 4.3278 pg/mL | Standard Error 0.75218 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | Baseline | 2.1626 pg/mL | Standard Error 0.67566 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 20min after CPT 1 | 2.7269 pg/mL | Standard Error 0.5303 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 50 min after CPT 1 | 2.7556 pg/mL | Standard Error 0.31272 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 20 min after CPT 2 | 3.8603 pg/mL | Standard Error 0.53619 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 50 min after CPT 2 | 3.3381 pg/mL | Standard Error 0.4539 |
| Insomnia Disorder | Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6 | 20 min after CPT 3 | 5.1606 pg/mL | Standard Error 0.95047 |
Primary
Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol
HPA marker: Change in serum cortisol levels (ug/dL)
Time frame: Baseline blood was obtained between 11am-12pm and prior to any Cold Pressor Tests (CPTs). Three CPTs were performed, with 1.5 hours between each one. The first CPT was done at 1pm. Blood draws were obtained 20min and 50 min after each CPT.
Population: Data of 3 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 50 min after CPT 1 | 8.3255 ug/dL | Standard Error 0.47898 |
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 50 min after CPT 2 | 6.452 ug/dL | Standard Error 0.39262 |
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 20min after CPT 1 | 10.6695 ug/dL | Standard Error 0.61099 |
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 20 min after CPT 3 | 8.7545 ug/dL | Standard Error 0.71965 |
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 20 min after CPT 2 | 8.448 ug/dL | Standard Error 0.57976 |
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 50 min after CPT 3 | 6.651 ug/dL | Standard Error 0.40265 |
| Healthy Controls | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | Baseline | 8.9948 ug/dL | Standard Error 1.00453 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 50 min after CPT 3 | 8.4684 ug/dL | Standard Error 1.01139 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | Baseline | 9.8250 ug/dL | Standard Error 0.92339 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 20min after CPT 1 | 13.95 ug/dL | Standard Error 1.22551 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 50 min after CPT 1 | 11.0416 ug/dL | Standard Error 0.95435 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 20 min after CPT 2 | 10.9342 ug/dL | Standard Error 1.13843 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 50 min after CPT 2 | 8.6063 ug/dL | Standard Error 0.98503 |
| Insomnia Disorder | Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol | 20 min after CPT 3 | 9.9168 ug/dL | Standard Error 1.27366 |
Secondary
Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes
Percentage of IL-6 positive monocytes following stimulation with LPS (100pg/mL) and varying concentrations of Dexamethasone
Time frame: Monocytes are only obtained from the baseline blood draw, which occurs at 11am.
Population: Data of 2 participants were excluded from analysis due to development of headache or Iv problems in the course of the experimental study day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Controls | Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes | 20.659 Percentage of IL-6 positive monocytes | Standard Error 2.9058 |
| Insomnia Disorder | Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes | 17.250 Percentage of IL-6 positive monocytes | Standard Error 1.9317 |