Hormonal Mechanisms of Sleep Restriction - Axis Study in Older Men and Postmenopausal Women

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-09

Study Completion Date

2026-06-24

Brief Summary

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The purpose of this study is to 1) determine how hypothalamic-pituitary-adrenal axis (HPA axis) activation occurs with sleep restriction and 2) evaluate how hypothalamic-pituitary-gonadal axis (HPG axis) deactivation occurs with sleep restriction. The investigator will also examine the cognitive function associated with sleep restriction, including food intake and food cravings.

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Detailed Description

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Sleep restriction and its consequences are major public health problems, especially in older adults. Among the more severe physiological sequelae of sleep restriction is the development of insulin resistance. The mechanisms by which sleep restriction leads to increased insulin resistance are unknown, especially in vulnerable older adults; such research informs development of targeted interventions against the sleep loss/insulin resistance link.

This study will administer drugs to clamp the function of each of these nodes to determine the regulatory changes that have occurred with sleep restriction. Even though the study is randomized order in design, the main comparison is before and after sleep restriction under each of these clamp conditions. Participants are admitted to the chronobiology laboratory where they are given 1 night of 10 hours sleep opportunity, followed by 4 nights of 4 hours sleep opportunity.

Up to 40 participants can be enrolled. However, participants will be allowed an opportunity to be randomized to all 4 conditions so that as few as 10 participants may be required. We anticipate 5 men and 5 women will be enrolled assuming each undergoes all 4 clamp conditions.

Conditions

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Sleep Restriction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Blood is sampled every 10 minutes from 4 pm to 9 pm for future mathematical deconvolution in order to determine hormone pulse characteristics in response to the clamp conditions.

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

3 of the 4 conditions are masked by use of identical injections and pills. However one condition (adrenal testis) is not masked. Hence the study is partially masked.

Study Groups

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Control Condition

8 am - Saline Solution for Injection

10 am - Placebo oral capsule

1 pm - Saline Solution for Injection

4 pm - Placebo oral capsule \& start hourly blood sampling

7 pm- Gonadorelin (GnRH) and Corticorelin (CRH) injections

9 pm - Saline Solution for Injection \& last blood sample

Group Type EXPERIMENTAL

Gonadorelin (also known as Lutrepulse)

Intervention Type DRUG

Gonadorelin IV injection is given twice per inpatient visit

Corticorelin (also known as Acthrel)

Intervention Type DRUG

Corticorelin IV injection is given twice per inpatient visit

Placebo oral tablet

Intervention Type DRUG

Placebo for Ketoconazole are given 4 times per inpatient visit

Saline Solution

Intervention Type DRUG

Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per inpatient visit

Saline solution for injection

Intervention Type DRUG

Saline Solution (placebo) for ganirelix subcutaneous injection

Hypothalamic Condition

8 am -Ganirelix

10 am - Placebo oral capsule

1 pm - Dexamethasone injection

4 pm- Placebo oral capsule and start of hourly blood sampling

7 pm - GnRH and CRH injections

9 pm - Saline Solution for Injection and last sample blood sample

Group Type EXPERIMENTAL

Ganirelix

Intervention Type DRUG

Ganirelix subcutaneous injection is administered twice per inpatient visit

Dexamethasone injection

Intervention Type DRUG

Dexamethasone IV injection is given twice per inpatient visit

Gonadorelin (also known as Lutrepulse)

Intervention Type DRUG

Gonadorelin IV injection is given twice per inpatient visit

Corticorelin (also known as Acthrel)

Intervention Type DRUG

Corticorelin IV injection is given twice per inpatient visit

Placebo oral tablet

Intervention Type DRUG

Placebo for Ketoconazole are given 4 times per inpatient visit

Saline solution for injection

Intervention Type DRUG

Saline Solution (placebo) for ganirelix subcutaneous injection

Pituitary Condition

8 am - Saline Solution for Injection

10 am - Ketoconazole Pill

1 pm - Saline Solution for Injection

4 pm - Ketoconazole Pill \& start of hourly blood sampling

7 pm - GnRH and CRH

9 pm - Hydrocortisone Injection and last blood sample

Group Type EXPERIMENTAL

Ketoconazole Pill (also known as nizoral)

Intervention Type DRUG

Ketoconazole pill is taken 4 times per inpatient visit

Hydrocortisone Injection (also known as solu-cortef)

Intervention Type DRUG

Hydrocortisone IV push is given twice per inpatient visit

Gonadorelin (also known as Lutrepulse)

Intervention Type DRUG

Gonadorelin IV injection is given twice per inpatient visit

Corticorelin (also known as Acthrel)

Intervention Type DRUG

Corticorelin IV injection is given twice per inpatient visit

Saline Solution

Intervention Type DRUG

Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per inpatient visit

Adrenal/Testis Condition

10 pm - Ganirelix Injection \& Dexamethasone Pills (night before)

8 am - Start of hourly blood sampling

10 am - Dexamethasone Pills

11 am - Last hourly blood sample taken

11:30 am - Start of blood sampling every 10 minutes

1 pm - Recombinant Human Luteinizing Hormone (rhLH) Injection

3 pm - rhLH Injection

5 pm - rhLH Injection

5 pm - Cosyntropin Injectable product

7 pm - GnRH and CRH Injections

9 pm - Last blood sample

Group Type EXPERIMENTAL

Ganirelix

Intervention Type DRUG

Ganirelix subcutaneous injection is administered twice per inpatient visit

Dexamethasone Pill

Intervention Type DRUG

Dexamethasone pills is taken twice per inpatient visit

Cosyntropin Injectable Product

Intervention Type DRUG

Cosyntropin injection is given twice per inpatient visit

Recombinant Human Luteinizing Hormone (also known as luveris)

Intervention Type DRUG

Recombinant Human Luteinizing Hormone is given as 6 IV infusion pulses per inpatient visit

Gonadorelin (also known as Lutrepulse)

Intervention Type DRUG

Gonadorelin IV injection is given twice per inpatient visit

Corticorelin (also known as Acthrel)

Intervention Type DRUG

Corticorelin IV injection is given twice per inpatient visit

Interventions

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Ketoconazole Pill (also known as nizoral)

Ketoconazole pill is taken 4 times per inpatient visit

Intervention Type DRUG

Ganirelix

Ganirelix subcutaneous injection is administered twice per inpatient visit

Intervention Type DRUG

Dexamethasone Pill

Dexamethasone pills is taken twice per inpatient visit

Intervention Type DRUG

Dexamethasone injection

Dexamethasone IV injection is given twice per inpatient visit

Intervention Type DRUG

Cosyntropin Injectable Product

Cosyntropin injection is given twice per inpatient visit

Intervention Type DRUG

Recombinant Human Luteinizing Hormone (also known as luveris)

Recombinant Human Luteinizing Hormone is given as 6 IV infusion pulses per inpatient visit

Intervention Type DRUG

Hydrocortisone Injection (also known as solu-cortef)

Hydrocortisone IV push is given twice per inpatient visit

Intervention Type DRUG

Gonadorelin (also known as Lutrepulse)

Gonadorelin IV injection is given twice per inpatient visit

Intervention Type DRUG

Corticorelin (also known as Acthrel)

Corticorelin IV injection is given twice per inpatient visit

Intervention Type DRUG

Placebo oral tablet

Placebo for Ketoconazole are given 4 times per inpatient visit

Intervention Type DRUG

Saline Solution

Saline Solution (Placebo) for Dexamethasone IV injection or hydrocortisone IV injection given up to four times per inpatient visit

Intervention Type DRUG

Saline solution for injection

Saline Solution (placebo) for ganirelix subcutaneous injection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Men or postmenopausal women aged 60-80 years
* Willingness to provide written informed consent
* Stable weight over preceding 6 weeks
* Body Mass index (BMI) 22-28 kg/m2
* Physically and psychologically healthy
* Good habitual sleep with regular bedtimes
* Neither extreme morning- nor extreme evening-type using Horne-Ostberg Morningness-Eveningness criteria

Exclusion Criteria

* Medications that interfere with the adrenal or gonadal axis will be excluded
* Unable or unwilling to provide IRB (Internal Review Board)-approved informed consent
* Clinical disorders and/or illnesses
* Current medical or drug treatment, as assessed by questionnaire
* History of brain injury or of learning disability
* Vision or hearing impairment unless corrected back to normal
* Anemia (Hct \<38%)
* History of psychiatric illness
* Clinically significant abnormalities in blood and urine, and free of traces of drugs
* Other endocrine abnormalities including hypothyroidism or adrenal failure; primary gonadal disease as indicated by serum LH (luteinizing hormone) or FSH (follicle stimulating hormone) concentration \>10 or \>15 IU/L, respectively, hyperprolactinemia indicated by prolactin \>25ug/L
* Type 2 Diabetes (HgbA1C)
* Current smoker
* Recent or concurrent drug or alcohol abuse
* Blood donation in previous eight weeks
* Travel across time zones within one month of entering the study
* Sleep or circadian disorder
* Shift work within three months of entering the study
* Irregular bedtimes (not between 6 and 10 hours in duration)
* Unoperated obstructive uropathy, recurrent prostatitis, indeterminate prostatic nodularity, Hx or Suspicion of cancer of the prostate gland or PSA (prostate-specific antigen) \>4ng/ml
* Previous adverse reaction to sleep deprivation or any of the drugs to be administered
* Concurrent participation in another research study
* Mini- mental state examination (MMSE) \< 27

Minimum Eligible Age

60 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes