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NCT Number: NCT00971815

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

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.

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Key information

Age range

20 year–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

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

Aarhus, 8000, Denmark

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

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

Treatment and study plan

Escitalopram

Drug

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

Drug

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

Primary outcomes

  1. Changes in rate of glucose dissappearance

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

  2. Changes in the 24-hour AUC of free plasma cortisol

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

Secondary outcomes

  1. 24 hour basal plasma cortisol/ACTH profile as measured every 3rd hour.

    Time frame: before and after 3 months of treatment with placebo or Escitalopram

  2. hippocampic volume and structure as assessed by MRI

    Time frame: 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.

  3. 24 hour bloodpressure profile

    Time frame: before and after 3 months of treatment with placebo or Escitalopram

  4. MRI spectroscopy of fat in skeletal muscle tissue

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  5. MRI spectroscopy of fat in liver

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  6. Abdominal fat as assessed by MRI

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  7. MDI questionnaire scores

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  8. SCL-92 questionnaire scores

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  9. Fasting blood lipid profile

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  10. Ratio between insulin and glucose concentrations in blood during an oral glucose tolerance test (OGTT)

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  11. Whole body fat content as assessed by a dexa scanning

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  12. Hepatic insulin sensitivity as assessed suppression of endogenous glucose production (calculated by infusion of 3H-labelled glucose)

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  13. 10 pm to midnight basal plasma ACTH/cortisol concentration ratio as measured by blood sampling every 10th minute.

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  14. increase in blood pressure and heart rate during Stroops Stress test

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  15. Increase in plasma ACTH, cortisol and epinephrine concentrations during Stroops Stress Test

    Time frame: before and after 3 months of treatment with placebo or Escitalopram

  16. SRPAS questionnaire scores

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

    Self Reported Physical Activity Questionaire

  17. Actigraph GT3X activity monitoring

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

    Objective measurements of physical activity in 96 hours at home

  18. Whole body bone mass density and T-/Z-scores as assessed by a dexa scanning

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

  19. Plasma-Inflammation markers

    Time frame: Before and after 3 months of treatment with placebo or Escitalopram

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Registry information

Official study 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

Acronym: LBW-SSRI

Important dates

Study start
2009
Primary completion
2011
Study completion
2014
First posted
Sep 4, 2009
Registry last updated
Jun 5, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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