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Do Serotonin Reuptake Inhibitors (SSRIs) Affect Bone Mass in Adolescents (SSRI_BMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02147184
Recruitment Status : Completed
First Posted : May 26, 2014
Results First Posted : October 24, 2017
Last Update Posted : October 24, 2017
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Chadi A. Calarge, University of Iowa

Brief Summary:
Building on findings from animal studies, pediatric clinical trials, epidemiologic research in adults, and on preliminary findings from the investigators' laboratory in children and adolescents, this project aims to investigate whether selective serotonin reuptake inhibitors (SSRIs), a group of widely-used psychotropics, are associated with impaired bone mineralization in youths. Establishing such an association is a first step in a process that would eventually involve developing preventative interventions. Identifying genetic factors that place certain youths at higher risks for this side effect would ultimately allow clinicians to tailor treatment to the needs and vulnerabilities of each youth, moving the field closer towards individualized medicine.

Condition or disease
The Skeletal Effects of SSRIs

Detailed Description:

Bone mass achieved by early adulthood is a major determinant of lifetime risk for osteoporosis. Therefore, optimizing peak bone mass is crucial to avoiding bone fracture with its associated morbidity and mortality.

Emerging evidence suggests that serotonin plays a central role in bone metabolism. For example, preclinical experiments have shown that bone cells express the serotonin transporter and a variety of functional serotonin receptors whose activity modulates bone turnover. Epidemiologic studies have linked SSRIs to reduced bone mineral density and increased fracture risk in the elderly. SSRIs are widely used in youths to treat a number of psychiatric disorders. However, while their short-term efficacy and safety have been established, their long-term safety remains little investigated.

The investigators aim to recruit, in a 2-year prospective observational study, 15 to 20 year-old participants upon the initiation of SSRI treatment. During the study period, bone mineral density of the lumbar spine and whole body will be measured using dual-energy x-ray absorptiometry (DXA) and of the radius using peripheral quantitative computed tomography (pQCT). A detailed psychiatric assessment will be conducted to control for psychopathology, as a potential confounding factor affecting bone mineralization. Changes in psychiatric treatment during the follow up period will also be documented and accounted for. By using a group of controls, of comparable age and sex distribution, the investigators aim to evaluate 1) whether psychopathology, at baseline, is associated with low bone mass, 2) if treatment with SSRIs suppresses bone mineralization, and 3) if the discontinuation of the SSRI is followed by a restoration of bone mineral accrual. 4) Furthermore, genetic testing will investigate whether variants of the serotonin system genes moderate the effect of SSRI treatment on bone mineral density.

In sum, this work aims to improve the long-term safety of psychiatric treatments in order to optimize functioning and the quality of life of those who suffer from psychiatric disorders.

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Study Type : Observational
Actual Enrollment : 287 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents
Actual Study Start Date : September 2010
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Minerals
Drug Information available for: Serotonin

Group/Cohort
SSRI Group
Participants within one month of starting an SSRI
Unmedicated Group
No treatment with SSRIs



Primary Outcome Measures :
  1. Total Body Less Head Bone Mineral Content (TBLH BMC) Z-score (Adjusted for Age-sex-height-race) [ Time Frame: At baseline and every 8 months up to 2 years. ]
    Whole-body dual energy x-ray absorptiometry (DXA) scan was obtained using a Hologic QDR DELPHI-4500A unit or a Hologic Discovery A unit (Hologic, Inc, Bedford, MA). The two DXA units were cross-calibrated.

  2. Trabecular Volumetric Bone Mineral Density at the Ultradistal Radius [ Time Frame: At baseline and every 4 months up to 2 years. ]
    Volumetric bone mineral density (vBMD) at the nondominant radius (4% and 20% sites) was measured, at study entry and every four months, with peripheral quantitative computed tomography (pQCT), using a Stratec XCT‐2000 scanner (Stratec, Inc., Pforzheim, Germany). Image analysis was performed using the manufacturer's software package, version 6.0. pQCT scans compromised by movement were rejected. Quality control and calibration of the equipment were performed daily.

  3. Osteocalcin to C-terminal Telopeptide Ratio [ Time Frame: At baseline and every 4 months up to 2 years. ]
    Osteocalcin (ng/mL) is a bone formation marker and C-terminal telopeptide (ng/mL) a marker of bone resorption.

  4. Bone-specific Alkaline Phosphatase to C-terminal Telopeptide Ratio [ Time Frame: At baseline and every 4 months up to 2 years. ]
    Bone-specific alkaline phosphatase (ng/mL) is a marker of bone formation while C-terminal telopeptide (ng/mL) is a marker of bone resorption.


Secondary Outcome Measures :
  1. Lumbar Spine Bone Mineral Density (BMD) Z-score [ Time Frame: At baseline and every 8 months up to 2 years. ]
    This is a Z-score adjusted for sex, age, race, and height.

  2. Cortical Volumetric BMD at 20% Radius [ Time Frame: At baseline and every 4 months up to 2 years. ]
  3. Cortical Thickness at 20% Radius [ Time Frame: At baseline and every 4 months up to 2 years. ]
    This is cortical thickness as measured by pQCT.


Other Outcome Measures:
  1. The Moderating Effect of the Short Allele of the Serotonin Transporter-Linked Polymorphic Region (5HTTLPR) Gene on the Association Between SSRI Use and the Primary Outcomes [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA
serum plasma DNA whole blood Stools Urine Paxgene


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients within one month of initiating treatment with SSRIs will be recruited, regardless of the indication for SSRIs.

Unmedicated controls will be also recruited.

Criteria

Inclusion Criteria:

  1. Age 15 to 20 years old (inclusive).
  2. Treatment with an SSRI, regardless of the indication, having been started within one month. This criterion does not apply to controls. SSRIs include: fluoxetine, citalopram, escitalopram, sertraline, paroxetine, and fluvoxamine.
  3. Ability to provide consent.

Exclusion Criteria:

  1. Age- and sex-adjusted height Z-score < -2 or > 2.
  2. Concomitant treatment with other antidepressants, psychostimulants, or mood stabilizers and antipsychotics. Treatment with benzodiazepines, low dose trazodone, alpha-2 agonists, and antihistaminergic agents will be allowed.
  3. Presence of illicit drug and/or alcohol dependence.
  4. Pregnancy.
  5. Primary bone diseases (e.g., Paget's disease, osteogenesis imperfecta, rheumatoid arthritis).
  6. Potential secondary bone disease (e.g., due to chronic inflammatory diseases, diabetes, hypo- or hyperparathyroidism, hyperthyroidism, growth hormone deficiency, and other endocrine disturbances, history of childhood cancer, or prior transplantation).
  7. Chronic disorders involving a vital organ (heart, lung, liver, kidney, brain) and congenital disorders.
  8. Malnutrition conditions (e.g., chronic diarrhea, inflammatory bowel disease) or lead poisoning.
  9. Chronic use of drugs affecting bone metabolism (e.g., oral corticosteroids).
  10. Inability to cooperate with the BMD measurements.
  11. Eating disorders, due to their potential effect on BMD.
  12. If a senior in high school, plan to join an out-of-state college.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02147184


Locations
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United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Chadi A. Calarge
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Chadi Calarge, MD University of Iowa

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Chadi A. Calarge, Principal Investigator, University of Iowa
ClinicalTrials.gov Identifier: NCT02147184    
Other Study ID Numbers: 201109866
R01MH090072-01A1 ( U.S. NIH Grant/Contract )
First Posted: May 26, 2014    Key Record Dates
Results First Posted: October 24, 2017
Last Update Posted: October 24, 2017
Last Verified: September 2017
Keywords provided by Chadi A. Calarge, University of Iowa:
SSRI
serotonin transporter
DXA
pQCT
bone mass
adolescents
Additional relevant MeSH terms:
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Serotonin
Serotonin Uptake Inhibitors
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators