Challenging the Inflammatory Response System in Insomnia Disorder

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02261597
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Duration (Months): 37.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Insomnia	Behavioral: Cold Pressor Test

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 44 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Challenging the Inflammatory Response System: Are Individuals With Insomnia More Reactive?
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Insomnia Disorder Testing reactivity of stress-related systems to repeated exposure to the cold pressor test (hand immersion into ice-cold water) among participants with a clinical diagnosis of insomnia disorder.	Behavioral: Cold Pressor Test; Repeated immersion of hand in ice-cold water
Healthy Control Testing reactivity of stress-related systems to repeated exposure to the cold pressor test (hand immersion into ice-cold water) among healthy participants without a diagnosis of insomnia disorder.	Behavioral: Cold Pressor Test; Repeated immersion of hand in ice-cold water

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BIDMC	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Haack Monika, PhD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 26, 2016

More Information

Publications

None provided.

• Responsible Party: Monika Haack, Assistant Professor of Neurology HMS, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT02261597
• Other Study ID Numbers: 2014P000297
• First Posted: Oct 10, 2014
• Last Update Posted: Jul 22, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Monika Haack, Assistant Professor of Neurology HMS, Beth Israel Deaconess Medical Center: insomnia, inflammation, stress
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders

Study Results

Participant Flow

Arm/Group Title	Healthy Controls	Insomnia Disorder
Arm/Group Description	Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen	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
Period Title: Overall Study
STARTED	22	22
COMPLETED	22	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Healthy Controls	Insomnia Disorder	Total
Arm/Group Description	Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen.	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.	Total of all reporting groups
Overall Participants	22	22	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 100%	22 100%	44 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	26.09	30.27	28.18
Sex: Female, Male (Count of Participants)
Female	19 86.4%	18 81.8%	37 84.1%
Male	3 13.6%	4 18.2%	7 15.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.5%	3 13.6%	4 9.1%
Not Hispanic or Latino	16 72.7%	12 54.5%	28 63.6%
Unknown or Not Reported	5 22.7%	7 31.8%	12 27.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	6 27.3%	2 9.1%	8 18.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 13.6%	0 0%	3 6.8%
White	11 50%	16 72.7%	27 61.4%
More than one race	1 4.5%	2 9.1%	3 6.8%
Unknown or Not Reported	1 4.5%	2 9.1%	3 6.8%
Region of Enrollment (participants) [Number]
United States	22 100%	22 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Inflammatory Response to Physiological Challenge- Change in Plasma Levels of IL-6
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Controls	Insomnia Disorder
Arm/Group Description	Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen	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
Measure Participants	21	20
Baseline	1.5013 (0.16892)	2.1626 (0.67566)
20min after CPT 1	2.5911 (0.49528)	2.7269 (0.5303)
50 min after CPT 1	3.0318 (0.55967)	2.7556 (0.31272)
20 min after CPT 2	3.7131 (0.65019)	3.8603 (0.53619)
50 min after CPT 2	4.2044 (0.64394)	3.3381 (0.4539)
20 min after CPT 3	5.514 (0.82173)	5.1606 (0.95047)
50 min after CPT 3	5.9841 (1.15086)	4.3278 (0.75218)

2. Primary Outcome

Title	Stress Reactivity to Physiological Challenge- Change in Serum Levels of Cortisol
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Controls	Insomnia Disorder
Arm/Group Description	Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen	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
Measure Participants	21	20
Baseline	8.9948 (1.00453)	9.8250 (0.92339)
20min after CPT 1	10.6695 (0.61099)	13.95 (1.22551)
50 min after CPT 1	8.3255 (0.47898)	11.0416 (0.95435)
20 min after CPT 2	8.448 (0.57976)	10.9342 (1.13843)
50 min after CPT 2	6.452 (0.39262)	8.6063 (0.98503)
20 min after CPT 3	8.7545 (0.71965)	9.9168 (1.27366)
50 min after CPT 3	6.651 (0.40265)	8.4684 (1.01139)

3. Secondary Outcome

Title	Glucocorticoid Sensitivity- Percentage of IL-6 Positive Monocytes
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Controls	Insomnia Disorder
Arm/Group Description	Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen	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
Measure Participants	22	20
Mean (Standard Error) [Percentage of IL-6 positive monocytes]	20.659 (2.9058)	17.250 (1.9317)

Adverse Events

Time Frame	Adverse event data were collected over a 9-hour period for each particpant.
Arm/Group Title	Healthy Controls		Insomnia Disorder
Arm/Group Description	Healthy participants without a diagnosis of insomnia disorder visited the CRC for a one-day stay immediately following an overnight sleep screen		Participants with the diagnosis of insomnia disorder (DSM-V) visited the CRC for a one-day stay immediately following an overnight sleep screen.
All Cause Mortality
	Healthy Controls		Insomnia Disorder
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Healthy Controls		Insomnia Disorder
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Controls		Insomnia Disorder
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.