Clinical trial NCT02599701: Acute Effects of Gabapentin in Sleep Parameters and Hormonal Release During Sleep in Older Men
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Sleep
Keywords: Delta Sleep
Growth Hormone
IGF-1
Lead sponsor: Associação Fundo de Incentivo à Pesquisa
Sponsor class: OTHER
First posted: 2015-11-09
Enrollment: 8
Sex: MALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Growth Hormone Secretion
timeFrame: During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
measure: IGF-1
timeFrame: Immediately after the sleep night in that gabapentin or placebo dose were given at bedtime.
Secondary outcomes:
measure: Total testosterone
timeFrame: During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
measure: Free testosterone
timeFrame: During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
measure: Cortisol
timeFrame: During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
measure: Apnea-Hypopnea Index during sleep
timeFrame: During only one sleep night immediately after a single gabapentin or placebo dose at bedtime. a single gabapentin or placebo dose at bedtime.
measure: Slow Wave Sleep - Stage N3
timeFrame: During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Instituto do Sono
Study officials:
affiliation: AFIP - Associação Fundo de Incentivo a Pesquisa
name: Sergio Tufik, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Rosenberg KP. Gabapentin for chronic insomnia. Am J Addict. 2003 May-Jun;12(3):273-4. No abstract available.