Acute Effects of Gabapentin in Sleep Parameters and Hormonal Release During Sleep in Older Men

Acute Effects of Gabapentin on Polysomnography Parameters and on Hypothalamic-pituitary-adrenal, Hypothalamic-pituitary-gonadal and Somatotropic Axes During Sleep in Older Men: a Randomized, Double-blind, Placebo-controlled Trial

The primary objective of this study is to evaluate the effects of gabapentin in sleep polysomnography parameters and in nocturnal secretion of endogenous hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG) and somatotropic axes hormones and basal IGF-1 in older men.

Study Overview

• Status: Terminated
• Conditions: Sleep
• Intervention / Treatment: Drug: Placebo; Drug: Gabapentin

Detailed Description

The influence of sleep variables on muscle protein anabolism is little studied, but data on the effects of slow-wave sleep and the syndrome of obstructive sleep apnea on the hypothalamic-pituitary axis indicate that interventions in the sleep structure and disorders impact on the age-related muscle loss. Thus, we propose to assess the acute effects of a drug potentially capable of increasing slow wave sleep, and consequently growth hormone release during sleep, on the physiological release of growth hormone, testosterone and IGF-1 during the night in older healthy men.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04024-002
    • Instituto do Sono

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 60 years old or more,
• healthy men

Exclusion Criteria:

• Basal Apnea-Hypopnea index (aHI)>=15
• Restless Legs Syndrome Symptons
• BMI less than 18.5 kg/m2 or greater than 30 kg/m2
• Less than 30 min. of regular physical activity (at least walking inside home, etc.)
• Plasma albumin below 3.5 mg/dL
• Psychoactive drugs use
• Drugs with muscle anabolic potential
• Current treatment for obesity or weight gain
• Enteral or parenteral feeding
• Inability to walk without assistance,
• Loss of independence in any activity of daily living
• Nocturia above 2 episodes
• Smoking more than 2 cigarettes per day
• Alcoholism (more than 2 doses a day)
• Prior epilepsy diagnosis
• Clinically evident atherosclerotic disease
• Dementia
• Depression
• Rheumatic diseases
• Cancer
• Diabetes (poorly controlled, HbA1C > 7,0, requirement of insulin)
• Thyroid dysfunction without treatment
• Advanced stages in COPD, HF, liver or renal failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; A single dose of placebo with exactly the same characteristics of the active drug at bedtime.	Drug: Placebo; A single placebo dose with the same physical characteristics of the active intervention.
Experimental: Gabapentin; A single dose of Gabapentin 300mg at bedtime.	Drug: Gabapentin; A single dose Gabapentin 300mg at bedtime.; Other Names: Neurontin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth Hormone Secretion	Every 20 minutes after admission to the laboratory, blood samples (2.5 mL) for GH measurement will be collected (between 20:00 - or 2 hours before lights off - and 06:00).	During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
IGF-1	It will be included in the analysis of the last sample collected for GH, testosterone and cortisol measurements at 06:00.	Immediately after the sleep night in that gabapentin or placebo dose were given at bedtime.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total testosterone	Every 20 minutes after admission to the laboratory, blood samples (2.5 mL) for free and total testosterone measurements will be collected (between 20:00 - or 2 hours before lights off - and 06:00).	During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
Free testosterone	Every 20 minutes after admission to the laboratory, blood samples (2.5 mL) for free and total testosterone measurements will be collected (between 20:00 - or 2 hours before lights off - and 06:00).	During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
Cortisol	Every 20 minutes after admission to the laboratory, blood samples (2.5 mL) for cortisol measurement will be collected (between 20:00 - or 2 hours before lights off - and 06:00).	During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
Apnea-Hypopnea Index during sleep	Sedative drugs may increase asymptomatic airway collapsability during sleep mainly in older individuals	During only one sleep night immediately after a single gabapentin or placebo dose at bedtime. a single gabapentin or placebo dose at bedtime.
Slow Wave Sleep - Stage N3	Full sleep night polysomnographic recording.	During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.

Collaborators and Investigators

• Sponsor: Associação Fundo de Incentivo à Pesquisa
• Investigators: Study Chair: Sergio Tufik, PhD, Afip - Associacao Fundo de Incentivo A Pesquisa

Publications and helpful links

General Publications

• Giannoulis MG, Martin FC, Nair KS, Umpleby AM, Sonksen P. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocr Rev. 2012 Jun;33(3):314-77. doi: 10.1210/er.2012-1002. Epub 2012 Mar 20.
• Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998 Dec;19(6):717-97. doi: 10.1210/edrv.19.6.0353.
• Dattilo M, Antunes HK, Medeiros A, Monico Neto M, Souza HS, Tufik S, de Mello MT. Sleep and muscle recovery: endocrinological and molecular basis for a new and promising hypothesis. Med Hypotheses. 2011 Aug;77(2):220-2. doi: 10.1016/j.mehy.2011.04.017. Epub 2011 May 7.
• Penev P, Spiegel K, L'Hermite-Baleriaux M, Schneider R, Van Cauter E. Relationship between REM sleep and testosterone secretion in older men. Ann Endocrinol (Paris). 2003 Apr;64(2):157. No abstract available.
• Van Cauter E, Latta F, Nedeltcheva A, Spiegel K, Leproult R, Vandenbril C, Weiss R, Mockel J, Legros JJ, Copinschi G. Reciprocal interactions between the GH axis and sleep. Growth Horm IGF Res. 2004 Jun;14 Suppl A:S10-7. doi: 10.1016/j.ghir.2004.03.006.
• Saletu M, Anderer P, Saletu-Zyhlarz GM, Parapatics S, Gruber G, Nia S, Saletu B. Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome. J Neural Transm (Vienna). 2010 Apr;117(4):463-73. doi: 10.1007/s00702-009-0361-3. Epub 2010 Jan 5.
• Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, Mascha E, Dinner D, Morris HH. Gabapentin increases slow-wave sleep in normal adults. Epilepsia. 2002 Dec;43(12):1493-7. doi: 10.1046/j.1528-1157.2002.21002.x.
• Rosenberg KP. Gabapentin for chronic insomnia. Am J Addict. 2003 May-Jun;12(3):273-4. No abstract available.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 21, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 9, 2015

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: July 12, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Growth Hormone; IGF-1; Delta Sleep
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: AFIP06/2015