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

Type 2 Diabetes Clinical Trial

— LBW-SSRI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00971815
• Other study ID #: M-20080132
• Status: Completed
• Phase: N/A
• First received: June 2, 2009
• Last updated: June 2, 2017
• Start date: May 2009
• Est. completion date: April 2014

Study information

• Verified date: May 2013
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2014
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Healthy men 20-35 years old.

2. birth weight <2500g.

3. Born at gestational week 38- 40 (42).

Exclusion Criteria:

1. Diabetes, insulin-resistance or precursors in first degree relatives or maternal gestational diabetes.

2. Small parents(mother <160cm and/or father <170cm).

3. History of abuse of alcohol, medicine og drugs in the mother during pregnancy.

4. Liver of renal failure : s-ALAT > 2.5 normal upper limit (>175µM) or s-creatinine >125 µmol/l.

5. Co-morbidity that after at medical examination is considered to be a problem.

6. BMI>25.5

7. Smoking that is considered to be an issue as regards completing the study.

8. Treatment with a MAO-inhibitor.

9. Born before gestational week 38.

10. Participation in larger X-ray examinations such CT-scans during the last 12 months.

11. Participation in medical experiments or treatments involving intravenous administration of radioactive substances during the last

12. Ongoing medical treatment that will be considered a issue for completing the study.

13. Allergy towards the substance Escitalopram.

14. Metal parts in the body that contra-indicates MRI.

15. Ongoing medical treatment thrombocyte inhibiting substances such as NSAIDS.

16. Previous gastrointestinal bleeding or gastro-duodenal ulcers.

17. Depression during examination or treatment

16/05-2011: Criterias updated - added 17 and adjusted 6. from BMI >25 to BMI >25.5

Related Conditions & MeSH terms

• Anxiety Disorders
• Birth Weight
• Body Weight
• Cardiovascular Disease
• Cardiovascular Diseases
• Insulin Resistance
• Low Birth Weight
• Melancholic Depression
• Type 2 Diabetes

Intervention

Drug:
• Escitalopram
first week: 10mg/day. Then, treatment with 20mg/day is continued throughout a 3 months period of time.
• placebo
1/2 pill pr day first week, then 1 pill pr. day throughout a 3 months treatment period (90-118 ± 7days)

Locations

Country	Name	City	State
Denmark	Medical Dep M, Diabetes and Endocrinology Aarhus University Hospital, Aarhus Sygehus	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in rate of glucose dissappearance		Changes in LBW-subjects from baseline vs. post-treatment after 3 months treatment with placebo or Escitalopram
Primary	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	24 hour basal plasma cortisol/ACTH profile as measured every 3rd hour.		before and after 3 months of treatment with placebo or Escitalopram
Secondary	hippocampic volume and structure as assessed by MRI	All limbic structures (amygdala, thalamus, hippocampus and ventromedial prefrontal cortex) were morphologically and volumetrically analyzed.	before and after 3 months of treatment with placebo or Escitalopram
Secondary	24 hour bloodpressure profile		before and after 3 months of treatment with placebo or Escitalopram
Secondary	MRI spectroscopy of fat in skeletal muscle tissue		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	MRI spectroscopy of fat in liver		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	Abdominal fat as assessed by MRI		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	MDI questionnaire scores		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	SCL-92 questionnaire scores		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	Fasting blood lipid profile		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	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
Secondary	Whole body fat content as assessed by a dexa scanning		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	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
Secondary	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
Secondary	increase in blood pressure and heart rate during Stroops Stress test		Before and after 3 months of treatment with placebo or Escitalopram
Secondary	Increase in plasma ACTH, cortisol and epinephrine concentrations during Stroops Stress Test		before and after 3 months of treatment with placebo or Escitalopram
Secondary	SRPAS questionnaire scores	Self Reported Physical Activity Questionaire	Before and after 3 months of treatment with placebo or Escitalopram
Secondary	Actigraph GT3X activity monitoring	Objective measurements of physical activity in 96 hours at home	Before and after 3 months of treatment with placebo or Escitalopram
Secondary	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
Secondary	Plasma-Inflammation markers		Before and after 3 months of treatment with placebo or Escitalopram