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 (LBW-SSRI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00971815
First received: June 2, 2009
Last updated: July 7, 2014
Last verified: May 2013
  Purpose

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 Intervention
Insulin Resistance
Low Birth Weight
Type 2 Diabetes
Cardiovascular Disease
Melancholic Depression
Anxiety Disorders
Drug: Escitalopram
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Hyperinsulinemic euglycemic clamp (m-value) [ Time Frame: Before and after 3 months treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • 24 hour urinary cortisol excretion [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • hippocampic volume and structure as assessed by MRI [ Time Frame: before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
    All limbic structures (amygdala, thalamus, hippocampus and ventromedial prefrontal cortex) were morphologically and volumetrically analyzed.

  • 24 hour bloodpressure profile [ Time Frame: before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • MRI spectroscopy of fat in skeletal muscle tissue [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • MRI spectroscopy of fat in liver [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • Abdominal fat as assessed by MRI [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • MDI questionnaire scores [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • SCL-92 questionnaire scores [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • Fasting blood lipid profile [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Whole body fat content as assessed by a dexa scanning [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • increase in blood pressure and heart rate during Stroops Stress test [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • SRPAS questionnaire scores [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
    Self Reported Physical Activity Questionaire

  • Actigraph GT3X activity monitoring [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
    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 [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]
  • Plasma-Inflammation markers [ Time Frame: Before and after 3 months of treatment with placebo or Escitalopram ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: May 2009
Study Completion Date: April 2014
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: no other names

  Eligibility

Ages Eligible for Study:   20 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00971815

Locations
Denmark
Medical Dep M, Diabetes and Endocrinology Aarhus University Hospital, Aarhus Sygehus
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
  More Information

No publications provided

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT00971815     History of Changes
Other Study ID Numbers: M-20080132
Study First Received: June 2, 2009
Last Updated: July 7, 2014
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: Danish Medicines Agency
Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
HPA-axis
fetal programming

Additional relevant MeSH terms:
Insulin Resistance
Birth Weight
Cardiovascular Diseases
Depression
Diabetes Mellitus, Type 2
Body Weight
Anxiety Disorders
Depressive Disorder
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Signs and Symptoms
Behavioral Symptoms
Diabetes Mellitus
Endocrine System Diseases
Mental Disorders
Mood Disorders
Dexetimide
Citalopram
Serotonin Uptake Inhibitors
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists

ClinicalTrials.gov processed this record on September 16, 2014