Effects of 3 Months of Selective Serotonin Reuptake Inhibitor (SSRI)-Treatment on Metabolism and Hypothalamic-pituitary-adrenal (HPA)-Axis in Young Men Born With Low Birth Weight

NCT00971815 | Completed DMC

• 1 other identifier: M-20080132
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic stress has been proposed to be involved the development of western life-style diseases such as cardiovascular disease and type 2 diabetes (T2DM). At the same time chronic stress is also believed to cause psychiatric disease such as melancholic depression (MD)and anxiety disorders. Accordingly, humans born with low birth weight (LBW) (ei. less than 5,0 LB) display an increased risk for T2DM and MD. Studies suggest stress and adrenal stress hormones (glucocorticoids) (GCC) might be involved in the development of both of these conditions. Recent studies of animals born LBW suggest, that SSRI-compounds, usually employed in the treatment of MD-related diseases, reduces stress-responses and levels of stress hormones such adrenal steroids and at the same time has a positive influence on glucose metabolism. In present study, the investigators aim to measure levels of GCC and stress and assess glucose metabolism in healthy young men (20-35 years) born LBW (40 subjects). The volume and structure of a certain brain area (ie. hippocampus) involved in regulation of adrenal GCC and known to be malfunctioning in chronically stressed individuals will be assessed by magnetic resonance imaging (MRI). Further metabolic examination will be accompanied by MRI spectroscopy of liver and muscle fat content as well as total fat content (Dexa-scanning) and contents of fat in the abdomen (by MRI) . Psychiatric well-ness and symptoms will be characterized by well-established questionnaires such as MDI and SCL-92 and responses as regards blood pressure, heart rate and changes in basal plasma concentrations of GCC and Epinephrine will be assessed while performing a Stroop Stress Test. Finally, a 24 hour blood pressure profile test will be included. After this extensive examination program, subjects will be randomized to 3-4 months of treatment with either Escitalopram (an SSRI-compound) or Placebo. Subsequently, at the end of the treatment, the whole examination program will be repeated to detect potential beneficial changes. A group of young normal birth weight men (20 subjects) will serve as a healthy baseline group for comparison and will not be exposed to any medical treatment. This trial will add understanding to the mechanism underlying the development of type 2 diabetes and depression in LBW. Additionally, present trial might be capable of proposing a novel treatment strategy to prevent the development of these diseases in LBW man.

Conditions

Insulin Resistance; Low Birth Weight; Type 2 Diabetes; Cardiovascular Disease; Melancholic Depression; Anxiety Disorders

Keywords

HPA-axis; fetal programming

Outcome Measures

Primary Outcomes (2)

• Changes in rate of glucose dissappearance

  Changes in LBW-subjects from baseline vs. post-treatment after 3 months treatment with placebo or Escitalopram

• Changes in the 24-hour AUC of free plasma cortisol

  Changes in LBW-subjects from baseline vs. post-treatment after 3 months treatment with placebo or Escitalopram

Secondary Outcomes (19)

• 24 hour basal plasma cortisol/ACTH profile as measured every 3rd hour.

  before and after 3 months of treatment with placebo or Escitalopram

• hippocampic volume and structure as assessed by MRI

  before and after 3 months of treatment with placebo or Escitalopram

• 24 hour bloodpressure profile

  before and after 3 months of treatment with placebo or Escitalopram

• MRI spectroscopy of fat in skeletal muscle tissue

  Before and after 3 months of treatment with placebo or Escitalopram

• MRI spectroscopy of fat in liver

  Before and after 3 months of treatment with placebo or Escitalopram

Study Arms (2)

escitalopram

ACTIVE COMPARATOR

A pill containing Escitalopram

Drug: Escitalopram

placebo

PLACEBO COMPARATOR

a placebo pill

Drug: placebo

Interventions

Escitalopram DRUG

first week: 10mg/day. Then, treatment with 20mg/day is continued throughout a 3 months period of time.

Also known as: Escitalopram (Cipralex)(H. Lundbeck A/S)

escitalopram

placebo DRUG

1/2 pill pr day first week, then 1 pill pr. day throughout a 3 months treatment period (90-118 ± 7days)

Also known as: no other names

placebo

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men 20-35 years old.
• birth weight \<2500g.
• Born at gestational week 38- 40 (42).

You may not qualify if:

• Diabetes, insulin-resistance or precursors in first degree relatives or maternal gestational diabetes.
• Small parents(mother \<160cm and/or father \<170cm).
• History of abuse of alcohol, medicine og drugs in the mother during pregnancy.
• Liver of renal failure : s-ALAT \> 2.5 normal upper limit (\>175μM) or s-creatinine \>125 μmol/l.
• Co-morbidity that after at medical examination is considered to be a problem.
• BMI\>25.5
• Smoking that is considered to be an issue as regards completing the study.
• Treatment with a MAO-inhibitor.
• Born before gestational week 38.
• Participation in larger X-ray examinations such CT-scans during the last 12 months.
• Participation in medical experiments or treatments involving intravenous administration of radioactive substances during the last
• Ongoing medical treatment that will be considered a issue for completing the study.
• Allergy towards the substance Escitalopram.
• Metal parts in the body that contra-indicates MRI.
• Ongoing medical treatment thrombocyte inhibiting substances such as NSAIDS.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Medical Dep M, Diabetes and Endocrinology Aarhus University Hospital, Aarhus Sygehus

Aarhus, 8000, Denmark

Location

Related Publications (1)

• Buhl CS, Stodkilde-Jorgensen H, Videbech P, Vaag A, Moller N, Lund S, Buhl ES. Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth Weight Men With Limbic Brain Alterations. J Clin Endocrinol Metab. 2018 Jan 1;103(1):115-124. doi: 10.1210/jc.2017-01438.

  PMID: 29053851 DERIVED

MeSH Terms

Conditions

Insulin Resistance; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Depressive Disorder; Anxiety Disorders

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2009
• First Posted: September 4, 2009
• Study Start: May 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: April 1, 2014
• Last Updated: June 5, 2017

Record last verified: 2013-05

Locations

DK (1)