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

• Sponsor: Associação Fundo de Incentivo à Pesquisa (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02599701
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 2.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep	Drug: Gabapentin; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Sep 1, 2015
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Growth Hormone Secretion [During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.]

   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).

2. IGF-1 [Immediately after the sleep night in that gabapentin or placebo dose were given at bedtime.]

   It will be included in the analysis of the last sample collected for GH, testosterone and cortisol measurements at 06:00.

Secondary Outcome Measures

1. Total testosterone [During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.]

   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).

2. Free testosterone [During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.]

   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).

3. Cortisol [During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.]

   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).

4. Apnea-Hypopnea Index during sleep [During only one sleep night immediately after a single gabapentin or placebo dose at bedtime. a single gabapentin or placebo dose at bedtime.]

   Sedative drugs may increase asymptomatic airway collapsability during sleep mainly in older individuals

5. Slow Wave Sleep - Stage N3 [During only one sleep night immediately after a single gabapentin or placebo dose at bedtime.]

   Full sleep night polysomnographic recording.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto do Sono	Sao Paulo		Brazil	04024-002

Sponsors and Collaborators

• Associação Fundo de Incentivo à Pesquisa

Investigators

• Study Chair: Sergio Tufik, PhD, AFIP - Associação Fundo de Incentivo a Pesquisa

Study Documents (Full-Text)

None provided.

More Information

Publications

• Dattilo M, Antunes HK, Medeiros A, Mônico 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.
• 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.
• 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. Review.
• 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. Review.
• Penev P, Spiegel K, L'Hermite-Balériaux M, Schneider R, Van Cauter E. Relationship between REM sleep and testosterone secretion in older men. Ann Endocrinol (Paris). 2003 Apr;64(2):157.
• Rosenberg KP. Gabapentin for chronic insomnia. Am J Addict. 2003 May-Jun;12(3):273-4.
• 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.
• 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. Review.

• Responsible Party: Dalva Poyares, Professor, Associação Fundo de Incentivo à Pesquisa
• ClinicalTrials.gov Identifier: NCT02599701
• Other Study ID Numbers: AFIP06/2015
• First Posted: Nov 9, 2015
• Last Update Posted: Jul 13, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Dalva Poyares, Professor, Associação Fundo de Incentivo à Pesquisa: Delta Sleep; Growth Hormone; IGF-1
• Additional relevant MeSH terms: Gabapentin

Study Results

No Results Posted as of Jul 13, 2016