Co-Feedback Action of Growth Hormone, PP and PYY on Ghrelin in Bulimia

Acipimox Administration Together With Short-Term Exercise Exerts A Co-Feedback of Growth Hormone, Pancreatic Polypeptide, Peptide YY and Leptin on Ghrelin in Young Bulimic Czech Women: A Randomized Study

This study evaluates the addition of Acipimox or placebo to exercise on growth hormone release and ghrelin secretion in bulimic patients and in healthy women. Two groups of participants will receive Acipimox together with exercise versus identical placebo with exercise.

Study Overview

• Status: Enrolling by invitation
• Conditions: Bulimia Nervosa; Eating Disorder
• Intervention / Treatment: Drug: Acipimox; Drug: Placebo

Detailed Description

Acipimox and exercise each increase growth hormone release, but they do so by different mechanisms.

Acipimox is an anti-lipolytic drug and increases growth hormone release by decreasing free fatty acids levels and that Acipimox may exert to a negative feedback of growth hormone on ghrelin.

Physical exercise is a potent physiological stimulus for growth hormone release. As ghrelin has a stimulatory effect on growth hormone secretion, growth hormone may inhibit circulating ghrelin levels via a feedback loop. Growth hormone stimulates lipolysis and resultant free fatty acids may suppress ghrelin secretion.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with a diagnosis of bulimia nervosa
• Body mass index (BMI) between 18 and 23 kg/m2

Exclusion Criteria:

• History of heart disease
• History of bleeding disorders
• Subjects with diabetes type 1 or 2, hypo- or hyperthyroidism
• Subjects with hepatogastroenteric disease
• Pregnant, trying to become pregnant or breast feeding
• Patients with other psychiatric diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acipimox; Other Names: Olbetam	Drug: Acipimox; Acipimox; Other Names: 5-methylpyrazine-2-carboxylic acid 4-oxide
Placebo Comparator: Placebo; Other Names: Placebo (for Olbetam)	Drug: Placebo; Placebo Other Names: Placebo (for Olbetam); Other Names: Cellulose pills manufactured to mimic Acipimox 250Mg Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma growth hormone levels	Plasma growth hormone (mIU/L) levels will be measured by a commercial RIA kit in the morning and after exercise alone or together with Acipimox administration over a total of 2 weeks.	baseline and over a total 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in extracellular adipose tissue glycerol levels	Extracellular adipose tissue glycerol (umol/L) levels will be measured using microdialysis technique and analyzed with a radiometric kit in the morning and after exercise alone or together with Acipimox administration over a total of 2 weeks.	baseline and over a total 2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in body mass index (BMI)	Weight in kilograms and height in meters will be measured in the morning and after exercise alone or together with Acipimox administration over a total of 2 weeks. Weight and height will be combined to report BMI in kg/m2.	baseline and over a total 2 weeks

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Investigators: Principal Investigator: Kvido Smitka, M.D., Ph.D., Charles University

Publications and helpful links

General Publications

• Nedvidkova J, Smitka K, Papezova H, Vondra K, Hill M, Hainer V. Acipimox during exercise points to an inhibitory feedback of GH on ghrelin secretion in bulimic and healthy women. Regul Pept. 2011 Feb 25;167(1):134-9. doi: 10.1016/j.regpep.2010.12.012. Epub 2011 Jan 13.
• Smitka K, Papezova H, Vondra K, Hill M, Hainer V, Nedvidkova J. A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study. Nutr Metab (Lond). 2011 Nov 17;8(1):81. doi: 10.1186/1743-7075-8-81.
• Smitka K, Papezova H, Vondra K, Hill M, Hainer V, Nedvidkova J. Short-term exercise combined with Acipimox administration induces an increase in plasma ACTH and its subsequent fall in the recovery phase in bulimic women. Regul Pept. 2013 Mar 10;182:45-52. doi: 10.1016/j.regpep.2012.12.010. Epub 2013 Jan 11.
• Smitka K, Papezova H, Vondra K, Hill M, Hainer V, Nedvidkova J. The role of "mixed" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: relevance to food intake and nutritional status in patients with anorexia nervosa and bulimia nervosa. Int J Endocrinol. 2013;2013:483145. doi: 10.1155/2013/483145. Epub 2013 Sep 9.
• Smitka K, Maresova D. Adipose Tissue as an Endocrine Organ: An Update on Pro-inflammatory and Anti-inflammatory Microenvironment. Prague Med Rep. 2015;116(2):87-111. doi: 10.14712/23362936.2015.49.
• Smitka K, Nedvidkova J, Vondra K, Hill M, Papezova H, Hainer V. Acipimox Administration With Exercise Induces a Co-feedback Action of the GH, PP, and PYY on Ghrelin Associated With a Reduction of Peripheral Lipolysis in Bulimic and Healthy-Weight Czech Women: A Randomized Study. Front Endocrinol (Lausanne). 2019 Mar 12;10:108. doi: 10.3389/fendo.2019.00108. eCollection 2019.
• Roubalova R, Prochazkova P, Papezova H, Smitka K, Bilej M, Tlaskalova-Hogenova H. Anorexia nervosa: Gut microbiota-immune-brain interactions. Clin Nutr. 2020 Mar;39(3):676-684. doi: 10.1016/j.clnu.2019.03.023. Epub 2019 Mar 23.
• Smitka K, Prochazkova P, Roubalova R, Dvorak J, Papezova H, Hill M, Pokorny J, Kittnar O, Bilej M, Tlaskalova-Hogenova H. Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders. Front Endocrinol (Lausanne). 2021 Apr 19;12:613983. doi: 10.3389/fendo.2021.613983. eCollection 2021.
• Prochazkova P, Roubalova R, Dvorak J, Kreisinger J, Hill M, Tlaskalova-Hogenova H, Tomasova P, Pelantova H, Cermakova M, Kuzma M, Bulant J, Bilej M, Smitka K, Lambertova A, Holanova P, Papezova H. The intestinal microbiota and metabolites in patients with anorexia nervosa. Gut Microbes. 2021 Jan-Dec;13(1):1-25. doi: 10.1080/19490976.2021.1902771.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2003
• Primary Completion (Actual): December 16, 2007
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 16, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: microdialysis; neuropeptides
• Additional Relevant MeSH Terms: Mental Disorders; Hyperphagia; Signs and Symptoms, Digestive; Bulimia; Feeding and Eating Disorders; Bulimia Nervosa; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Acipimox
• Other Study ID Numbers: AZV Grant Agency

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No