Hormonal Mechanisms of Sleep Restriction - Axis Study

Peter y. Liu

Status and phase: Active, not recruiting; Phase 1

Conditions: Sleep Restriction

Treatments: Drug: Recombinant Human Luteinizing Hormone; Drug: Ketoconazole Pill; Drug: Hydrocortisone Injection; Drug: Placebo oral capsule; Drug: Dexamethasone Injection; Drug: Dexamethasone; Drug: Ganirelix; Drug: Cosyntropin Injectable Product; Drug: Gonadorelin; Drug: Saline Solution; Drug: Corticorelin; Drug: Saline Solution for Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT03142893

30068-01A

Details and patient eligibility

About

The purpose of this study is to 1) determine how hypothalamic-pituitary-adrenal axis (HPA axis) activation occurs with sleep restriction 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.

Full description

Sleep restriction increases evening cortisol and decreases testosterone. These are the main catabolic and anabolic hormones in men, respectively. This catabolic-anabolic imbalance likely leads to metabolic and reproductive ill-health. The hypothalamic-pituitary-end organ (adrenal or testis) mechanisms that must underpin these changes are unknown. 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 80 participants (assuming twenty different participant for each of the 4 clamp conditions) can be enrolled. However, participants will be allowed an opportunity to be randomized to all 4 conditions so that as few as 20 participants may be required. Urn randomization will be used to ensure that 20 different participants are involved in each of the 4 conditions.

Enrollment: 80 estimated patients

Sex: Male

Ages: 22 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Men aged 22-45 years
• Willingness to provide written informed consent
• Stable weight over preceding 6 weeks
• Body Mass index (BMI) 20-28 kg/m2

Exclusion criteria

• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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80 participants in 4 patient groups

Control Condition

Experimental group

Description:

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

Treatment:

Drug: Saline Solution for Injection

Drug: Placebo oral capsule

Drug: Corticorelin

Drug: Saline Solution

Drug: Gonadorelin

Hypothalamic Condition

Experimental group

Description:

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 of blood taken

Treatment:

Drug: Dexamethasone Injection

Drug: Saline Solution for Injection

Drug: Placebo oral capsule

Drug: Corticorelin

Drug: Gonadorelin

Drug: Ganirelix

Pituitary Condition

Experimental group

Description:

8am - Saline Solution for Injection 10am - Ketoconazole Pill 1pm - Saline Solution for Injection 4pm - Ketoconazole Pill \& start of hourly blood sampling 7pm - GnRH and CRH 9pm - Hydrocortisone Injection \& last blood sample

Treatment:

Drug: Hydrocortisone Injection

Drug: Corticorelin

Drug: Saline Solution

Drug: Gonadorelin

Drug: Ketoconazole Pill

Adrenal/Testis Condition

Experimental group

Description:

10pm - Ganirelix Injection \& Dexamethasone Pills (night before) 8am - start of hourly blood sampling 10am - Dexamethasone Pills 11am - last hourly blood sample taken 11:30am - start of blood sampling every 10 minutes 1pm - Recombinant Human Luteinizing Hormone (rhLH) Injection 3pm - rhLH Injection 5pm - rhLH Injection 5pm - Cosyntropin Injectable product 7pm - GnRH and CRH Injections 9pm - last blood sample taken

Treatment:

Drug: Dexamethasone

Drug: Corticorelin

Drug: Gonadorelin

Drug: Recombinant Human Luteinizing Hormone

Drug: Cosyntropin Injectable Product

Drug: Ganirelix