The Skeletal Effects of SSRIsSSRI_BMDNCT02147184
Do Serotonin Reuptake Inhibitors (SSRIs) Affect Bone Mass in Adolescents
An observational study of The Skeletal Effects of SSRIs, run by Chadi A. Calarge at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- The Skeletal Effects of SSRIs
- How many people
- 287 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Apr 2016
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- Age 15 to 20 years old (inclusive).
- 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.
- Ability to provide consent.
Who cannot join
- Age- and sex-adjusted height Z-score < -2 or > 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.
- Presence of illicit drug and/or alcohol dependence.
- Pregnancy.
- Primary bone diseases (e.g., Paget's disease, osteogenesis imperfecta, rheumatoid arthritis).
- 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).
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- Chronic disorders involving a vital organ (heart, lung, liver, kidney, brain) and congenital disorders.
- Malnutrition conditions (e.g., chronic diarrhea, inflammatory bowel disease) or lead poisoning.
- Chronic use of drugs affecting bone metabolism (e.g., oral corticosteroids).
- Inability to cooperate with the BMD measurements.
- Eating disorders, due to their potential effect on BMD.
- If a senior in high school, plan to join an out-of-state college.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
Official title: Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents
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.
Read the 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.
- Conditions
- The Skeletal Effects of SSRIs
- Keywords
- SSRI, serotonin transporter, DXA, pQCT, bone mass, adolescents
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SSRI Group | Participants within one month of starting an SSRI | |
| Unmedicated Group | No treatment with SSRIs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Body Less Head Bone Mineral Content (TBLH BMC) Z-score (Adjusted for Age-sex-height-race)
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.
Measured: At baseline and every 8 months up to 2 years.
Trabecular Volumetric Bone Mineral Density at the Ultradistal Radius
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.
Measured: At baseline and every 4 months up to 2 years.
Osteocalcin to C-terminal Telopeptide Ratio
Osteocalcin (ng/mL) is a bone formation marker and C-terminal telopeptide (ng/mL) a marker of bone resorption.
Measured: At baseline and every 4 months up to 2 years.
Bone-specific Alkaline Phosphatase to C-terminal Telopeptide Ratio
Bone-specific alkaline phosphatase (ng/mL) is a marker of bone formation while C-terminal telopeptide (ng/mL) is a marker of bone resorption.
Measured: At baseline and every 4 months up to 2 years.
Secondary outcomes (3)
Lumbar Spine Bone Mineral Density (BMD) Z-score
This is a Z-score adjusted for sex, age, race, and height.
Measured: At baseline and every 8 months up to 2 years.
Cortical Volumetric BMD at 20% Radius
Measured: At baseline and every 4 months up to 2 years.
Cortical Thickness at 20% Radius
This is cortical thickness as measured by pQCT.
Measured: At baseline and every 4 months up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2014 (estimated)
- Study startSep 2010
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for The Skeletal Effects of SSRIsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 287 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chadi A. Calarge
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Chadi A. Calarge, University of Iowa
- Investigators
- Chadi Calarge, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02147184
- Sponsor's protocol ID
- 201109866
- Other IDs
- R01MH090072-01A1
- Acronym
- SSRI_BMD
- Status last verified
- Jun 2023
- First submitted
- 2 Apr 2014
- Last updated
- 28 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ezenwabachili I, Deumic Shultz E, Mills JA, Ellingrod V, Calarge CA. Examining Whether Genetic Variants Moderate the Skeletal Effects of Selective Serotonin Reuptake Inhibitors in Older Adolescents and Young Adults. J Child Adolesc Psychopharmacol. 2023 Sep;33(7):260-268. doi: 10.1089/cap.2023.0007. Epub 2023 Aug 9.
PubMed 37579130Martins LB, Delevati Colpo G, Calarge CA, Teixeira AL. Inflammatory Markers Profile in Older Adolescents During Treatment with Selective Serotonin Reuptake Inhibitors. J Child Adolesc Psychopharmacol. 2021 Aug;31(6):439-444. doi: 10.1089/cap.2020.0140. Epub 2021 Jun 24.
PubMed 34166063Mellick WH, Mills JA, Kroska EB, Calarge CA, Sharp C, Dindo LN. Experiential Avoidance Predicts Persistence of Major Depressive Disorder and Generalized Anxiety Disorder in Late Adolescence. J Clin Psychiatry. 2019 Oct 22;80(6):18m12265. doi: 10.4088/JCP.18m12265.
PubMed 31644841Dindo LN, Recober A, Haddad R, Calarge CA. Comorbidity of Migraine, Major Depressive Disorder, and Generalized Anxiety Disorder in Adolescents and Young Adults. Int J Behav Med. 2017 Aug;24(4):528-534. doi: 10.1007/s12529-016-9620-5.
PubMed 28032323Deumic E, Butcher BD, Clayton AD, Dindo LN, Burns TL, Calarge CA. Sexual Functioning in Adolescents With Major Depressive Disorder. J Clin Psychiatry. 2016 Jul;77(7):957-62. doi: 10.4088/JCP.15m09840.
PubMed 27464316
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents
- ClinicalTrials.gov ID
- NCT02147184
- Acronym / sponsor ID
- SSRI_BMD / 201109866
- Conditions
- The Skeletal Effects of SSRIs
- Keywords
- SSRI, serotonin transporter, DXA, pQCT, bone mass, adolescents
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 287 participants (actual)
- Lead sponsor
- Chadi A. CalargeUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Sep 2010 (actual)
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 26 May 2014 (estimated)
- Results
- Posted 24 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SSRI Group | – | –Participants within one month of starting an SSRI |
| Unmedicated Group | – | –No treatment with SSRIs |
Who may qualify
- Ages
- 15 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (3 listed)
- Age 15 to 20 years old (inclusive).
- 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.
- Ability to provide consent.
Key exclusion criteria (12 listed)
- Age- and sex-adjusted height Z-score < -2 or > 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.
- Presence of illicit drug and/or alcohol dependence.
- Pregnancy.
- Primary bone diseases (e.g., Paget's disease, osteogenesis imperfecta, rheumatoid arthritis).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
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.
3 secondary outcomes
Lumbar Spine Bone Mineral Density (BMD) Z-score
Time frame: At baseline and every 8 months up to 2 years.
Cortical Volumetric BMD at 20% Radius
Time frame: At baseline and every 4 months up to 2 years.
Cortical Thickness at 20% Radius
Time frame: At baseline and every 4 months up to 2 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37579130Ezenwabachili I, Deumic Shultz E, Mills JA, Ellingrod V, Calarge CA. Examining Whether Genetic Variants Moderate the Skeletal Effects of Selective Serotonin Reuptake Inhibitors in Older Adolescents and Young Adults. J Child Adolesc Psychopharmacol. 2023 Sep;33(7):260-268. doi: 10.1089/cap.2023.0007. Epub 2023 Aug 9.
- Derived from this study: PubMed 34166063Martins LB, Delevati Colpo G, Calarge CA, Teixeira AL. Inflammatory Markers Profile in Older Adolescents During Treatment with Selective Serotonin Reuptake Inhibitors. J Child Adolesc Psychopharmacol. 2021 Aug;31(6):439-444. doi: 10.1089/cap.2020.0140. Epub 2021 Jun 24.
- Derived from this study: PubMed 31644841Mellick WH, Mills JA, Kroska EB, Calarge CA, Sharp C, Dindo LN. Experiential Avoidance Predicts Persistence of Major Depressive Disorder and Generalized Anxiety Disorder in Late Adolescence. J Clin Psychiatry. 2019 Oct 22;80(6):18m12265. doi: 10.4088/JCP.18m12265.
- Derived from this study: PubMed 28032323Dindo LN, Recober A, Haddad R, Calarge CA. Comorbidity of Migraine, Major Depressive Disorder, and Generalized Anxiety Disorder in Adolescents and Young Adults. Int J Behav Med. 2017 Aug;24(4):528-534. doi: 10.1007/s12529-016-9620-5.
- Derived from this study: PubMed 27464316Deumic E, Butcher BD, Clayton AD, Dindo LN, Burns TL, Calarge CA. Sexual Functioning in Adolescents With Major Depressive Disorder. J Clin Psychiatry. 2016 Jul;77(7):957-62. doi: 10.4088/JCP.15m09840.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chadi Calarge, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of The Skeletal Effects of SSRIs, run by Chadi A. Calarge at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02147184, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.