LBW-SSRI: 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

Sponsor

University of Aarhus (Other)

Overall Status

Completed

CT.gov ID

NCT00971815

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance Low Birth Weight Type 2 Diabetes Cardiovascular Disease Melancholic Depression Anxiety Disorders	Drug: Escitalopram Drug: placebo	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Effects of 3 Months of SSRI-Treatment on Metabolism and HPA-axis in Young Men Born With Low Birth Weight - a Randomized, Double Blinded and Placebo-controlled Trial

Study Start Date :

May 1, 2009

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: escitalopram A pill containing Escitalopram	Drug: Escitalopram first week: 10mg/day. Then, treatment with 20mg/day is continued throughout a 3 months period of time. Other Names: Escitalopram (Cipralex)(H. Lundbeck A/S)
Placebo Comparator: placebo a placebo pill	Drug: placebo 1/2 pill pr day first week, then 1 pill pr. day throughout a 3 months treatment period (90-118 ± 7days) Other Names: no other names

Arm

Intervention/Treatment

Active Comparator: escitalopram

A pill containing Escitalopram

Drug: Escitalopram

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

Other Names:

Escitalopram (Cipralex)(H. Lundbeck A/S)

Placebo Comparator: placebo

a placebo pill

Drug: placebo

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

Other Names:

no other names

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
All limbic structures (amygdala, thalamus, hippocampus and ventromedial prefrontal cortex) were morphologically and volumetrically analyzed.
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]
Abdominal fat as assessed by MRI [Before and after 3 months of treatment with placebo or Escitalopram]
MDI questionnaire scores [Before and after 3 months of treatment with placebo or Escitalopram]
SCL-92 questionnaire scores [Before and after 3 months of treatment with placebo or Escitalopram]
Fasting blood lipid profile [Before and after 3 months of treatment with placebo or Escitalopram]
Ratio between insulin and glucose concentrations in blood during an oral glucose tolerance test (OGTT) [Before and after 3 months of treatment with placebo or Escitalopram]
Whole body fat content as assessed by a dexa scanning [Before and after 3 months of treatment with placebo or Escitalopram]
Hepatic insulin sensitivity as assessed suppression of endogenous glucose production (calculated by infusion of 3H-labelled glucose) [Before and after 3 months of treatment with placebo or Escitalopram]
10 pm to midnight basal plasma ACTH/cortisol concentration ratio as measured by blood sampling every 10th minute. [Before and after 3 months of treatment with placebo or Escitalopram]
increase in blood pressure and heart rate during Stroops Stress test [Before and after 3 months of treatment with placebo or Escitalopram]
Increase in plasma ACTH, cortisol and epinephrine concentrations during Stroops Stress Test [before and after 3 months of treatment with placebo or Escitalopram]
SRPAS questionnaire scores [Before and after 3 months of treatment with placebo or Escitalopram]
Self Reported Physical Activity Questionaire
Actigraph GT3X activity monitoring [Before and after 3 months of treatment with placebo or Escitalopram]
Objective measurements of physical activity in 96 hours at home
Whole body bone mass density and T-/Z-scores as assessed by a dexa scanning [Before and after 3 months of treatment with placebo or Escitalopram]
Plasma-Inflammation markers [Before and after 3 months of treatment with placebo or Escitalopram]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 35 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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.
Previous gastrointestinal bleeding or gastro-duodenal ulcers.
Depression during examination or treatment