Calcium and Vitamin D to Optimize Bone Mass in Boys With Risperidone-induced Hyperprolactinemia

Sponsor
Chadi A. Calarge (Other)
Overall Status
Completed
CT.gov ID
NCT00799383
Collaborator
National Institute of Mental Health (NIMH) (NIH), Children's Miracle Network (Other)
47
1
2
63.9
0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether calcium and vitamin D supplementation, over a nine-month period, optimizes bone mineralization in boys with risperidone-induced hyperprolactinemia. We hypothesize that, by the end of the stuy, children in the supplementation group will have higher bone mineral density compared to those in the placebo group.

Condition or Disease Intervention/Treatment Phase
  • Drug: Calcium and Vitamin D
  • Other: Placebo
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Counteracting Risperidone-Induced Hyperprolactinemia in Youths
Study Start Date :
Nov 1, 2008
Actual Primary Completion Date :
Mar 1, 2014
Actual Study Completion Date :
Mar 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Calcium and Vitamin D

Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period.

Drug: Calcium and Vitamin D
Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period.
Other Names:
  • Ca+VitD
  • Placebo Comparator: Placebo

    Placebo

    Other: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Trabecular Bone Mineral Density in the Ultradistal Radius [36 weeks]

      Peripheral quantitative computed tomography (pQCT) scan was obtained at the 4% and 20% sites of the nondominant radius to estimate trabecular and cortical BMD, respectively. A Stratec XCT-2000 scanner, software version 6.0 (Stratec, Inc., Pforzheim, Germany),was used. Trabecular BMD was measured as the mean density of the 85% central area of the bone's cross-section. Outcomes were measured at baseline, 18 weeks, and 36 weeks later.

    2. Total Body Bone Mineral Content [36 weeks]

      Outcomes were measured at baseline, 18 weeks, and 36 weeks later.

    Secondary Outcome Measures

    1. Bone Strength Index, mg2/mm4 [36 weeks]

      Measured at the 4% radius site.

    2. Cortical Bone Mineral Density [36 weeks]

      This was measured at the 20% radius site.

    3. Cortical Thickness [36 weeks]

      This was measured at the 20% radius site.

    4. Periosteal Circumference [36 weeks]

      This was measured at the 20% radius site.

    5. Endosteal Circumference [36 weeks]

      This was measured at the 20% radius site.

    6. Polar Section Modulus [36 weeks]

      This was measured at the 20% radius site.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years to 17 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Males (age range: 5-17yo; inclusive), in treatment with risperidone for ≥ one year.

    2. The participants must have two measurements of prolactin ≥ 18.4 ng/ml, obtained within a week.

    3. IQ > 35-40 (≥ Moderate intellectual disability).

    4. An adult parent/guardian must be available to provide consent and dispense study medication.

    Exclusion Criteria:
    1. Chronic disorders involving a vital organ (heart, lung, liver, kidney, brain), metabolic diseases (e.g., diabetes, hypo- or hyperparathyroidism, hypo- or hyperthyroidism, growth hormone deficiency), other skeletal diseases (e.g., Paget's disease, osteogenesis imperfecta, rheumatoid arthritis), chronic use of drugs affecting bone metabolism (e.g., corticosteroids), and malnutrition conditions (e.g., chronic diarrhea, inflammatory bowel disease), congenital disorders, or lead poisoning.

    2. Participants receiving calcium or multivitamins in the previous three months.

    3. A history of renal calculi and fasting random urine calcium/creatinine ratio > 0.2 or any other medical disorder that contraindicates the use of calcium or vitamin D (e.g., hypercalcemic states, hypercoagulability disorders, vitamin D toxicity, malabsorption syndrome, or hypersensitivity to vitamin D products).

    4. Laboratory values outside the normal range, except for prolactin, unless the deviations were not clinically significant (e.g. TSH < 10 μIU/ml (76)).

    5. Inability to cooperate with the BMD measurements.

    6. Bilateral wrist or forearm fractures.

    7. Eating disorders.

    8. Non-compliance with the prescribed psychiatric treatment as reflected by an undetectable combined risperidone and 9-hydroxy risperidone blood concentration.

    9. Plans to move out of State within the next 9 months.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The University of Iowa Iowa City Iowa United States 52242

    Sponsors and Collaborators

    • Chadi A. Calarge
    • National Institute of Mental Health (NIMH)
    • Children's Miracle Network

    Investigators

    • Principal Investigator: Chadi Calarge, M.D., University of Iowa

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chadi A. Calarge, Principal Investigator, University of Iowa
    ClinicalTrials.gov Identifier:
    NCT00799383
    Other Study ID Numbers:
    • 200807730
    • K23MH085005
    First Posted:
    Nov 27, 2008
    Last Update Posted:
    Dec 26, 2017
    Last Verified:
    Nov 1, 2017
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Chadi A. Calarge, Principal Investigator, University of Iowa
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Between 02/2009 and 11/2013, medically-healthy 5 to 17 year-old risperidone-treated boys were enrolled, via screening of the electronic medical records, referrals, and word of mouth.
    Pre-assignment Detail Participants were required to have been in treatment with risperidone for at least one year. They should have had a prolactin concentration ≥ 18.4 ng/ml on two occasions, within one week.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. Placebo administered in similarly looking capsules.
    Period Title: Overall Study
    STARTED 23 24
    COMPLETED 20 18
    NOT COMPLETED 3 6

    Baseline Characteristics

    Arm/Group Title Calcium+VitD Placebo Total
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Total of all reporting groups
    Overall Participants 23 24 47
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    10.8
    (3.0)
    12.1
    (3.0)
    11.5
    (3.0)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    23
    100%
    24
    100%
    47
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    8.7%
    0
    0%
    2
    4.3%
    Not Hispanic or Latino
    21
    91.3%
    24
    100%
    45
    95.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    4.3%
    5
    20.8%
    6
    12.8%
    White
    21
    91.3%
    19
    79.2%
    40
    85.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    4.3%
    0
    0%
    1
    2.1%
    Total Body Less Head Bone Mineral Content Z-score (Z-score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Z-score]
    0.10
    (0.79)
    0.12
    (0.68)
    0.11
    (0.73)
    Trabecular Bone Mineral Density, mg/cm3 (mg/cm3) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/cm3]
    192.9
    (31.1)
    197.2
    (43.9)
    195.0
    (37.5)

    Outcome Measures

    1. Primary Outcome
    Title Trabecular Bone Mineral Density in the Ultradistal Radius
    Description Peripheral quantitative computed tomography (pQCT) scan was obtained at the 4% and 20% sites of the nondominant radius to estimate trabecular and cortical BMD, respectively. A Stratec XCT-2000 scanner, software version 6.0 (Stratec, Inc., Pforzheim, Germany),was used. Trabecular BMD was measured as the mean density of the 85% central area of the bone's cross-section. Outcomes were measured at baseline, 18 weeks, and 36 weeks later.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    The number at baseline is smaller than the randomized number because bone scans with movement artifact were discarded. At late time points, the sample size reflects both attrition and exclusion due to movement artifact.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 22 21
    Baseline
    192.9
    (31.1)
    197.2
    (43.9)
    At 18 Weeks
    191.0
    (38.4)
    194.6
    (41.2)
    At 36 Weeks
    195.7
    (36.9)
    213.1
    (42.1)
    2. Primary Outcome
    Title Total Body Bone Mineral Content
    Description Outcomes were measured at baseline, 18 weeks, and 36 weeks later.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Numbers below reflect attrition.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 23 24
    At Baseline
    0.10
    (0.79)
    0.12
    (0.68)
    At 18 Weeks
    0.24
    (0.81)
    0.23
    (0.76)
    At 36 Weeks
    0.20
    (0.86)
    0.17
    (0.78)
    3. Secondary Outcome
    Title Bone Strength Index, mg2/mm4
    Description Measured at the 4% radius site.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Sample size is smaller because scans with movement artifact were removed at baseline. At follow up, attrition also contributed.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 22 21
    Baseline
    19.8
    (8.1)
    25.3
    (15.9)
    week 18
    21.0
    (9.1)
    22.9
    (14.3)
    week 36
    23.1
    (9.6)
    26.1
    (14.5)
    4. Secondary Outcome
    Title Cortical Bone Mineral Density
    Description This was measured at the 20% radius site.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Sample size reduced due to exclusion of scans with movement artifact and, in later visits, due to attrition as well.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 18 20
    Baseline
    1059.6
    (34.8)
    1063.2
    (30.6)
    week 18
    1062.8
    (34.5)
    1060.2
    (27.1)
    week 36
    1069.3
    (31.8)
    1058.7
    (27.4)
    5. Secondary Outcome
    Title Cortical Thickness
    Description This was measured at the 20% radius site.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Sample size reduced due to exclusion of scans with movement artifact and, in later visits, due to attrition as well.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 18 20
    Baseline
    2.25
    (0.32)
    2.34
    (0.50)
    week 18
    2.25
    (0.34)
    2.26
    (0.45)
    week 36
    2.32
    (0.35)
    2.34
    (0.44)
    6. Secondary Outcome
    Title Periosteal Circumference
    Description This was measured at the 20% radius site.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Sample size reduced due to exclusion of scans with movement artifact and, in later visits, due to attrition as well.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 18 20
    Baseline
    30.1
    (4.3)
    32.4
    (5.4)
    week 18
    31.2
    (4.3)
    32.6
    (6.1)
    week 36
    31.4
    (4.0)
    32.3
    (5.1)
    7. Secondary Outcome
    Title Endosteal Circumference
    Description This was measured at the 20% radius site.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Sample size reduced due to exclusion of scans with movement artifact and, in later visits, due to attrition as well.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 18 20
    Baseline
    16.0
    (3.4)
    17.7
    (3.6)
    week 18
    17.0
    (3.9)
    18.4
    (5.1)
    week 36
    16.8
    (3.7)
    17.6
    (4.0)
    8. Secondary Outcome
    Title Polar Section Modulus
    Description This was measured at the 20% radius site.
    Time Frame 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Sample size reduced due to exclusion of scans with movement artifact and, in later visits, due to attrition as well.
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    Measure Participants 18 20
    Baseline
    123.8
    (53.6)
    156.2
    (76.6)
    week 18
    134.5
    (55.1)
    156.8
    (91.9)
    week 36
    137.2
    (49.2)
    151.9
    (75.6)

    Adverse Events

    Time Frame Data collected during 36 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Calcium+VitD Placebo
    Arm/Group Description Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic. Calcium and Vitamin D: Calcium carbonate 625mg and vitamin D 200IU will be administered, orally, twice a day for a nine-month period. I labelled the intervention type as "drug", even though "dietary supplement" would be more appropriate as the system sent the following error message: ERROR: An IND/IDE study must have at least one intervention of type: Drug, Device, Biological/Vaccine, Radiation or Genetic.
    All Cause Mortality
    Calcium+VitD Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/24 (0%)
    Serious Adverse Events
    Calcium+VitD Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/24 (0%)
    Other (Not Including Serious) Adverse Events
    Calcium+VitD Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/23 (47.8%) 8/24 (33.3%)
    Gastrointestinal disorders
    Stomach ache 5/23 (21.7%) 5 3/24 (12.5%) 3
    Bloating 1/23 (4.3%) 1 0/24 (0%) 0
    Nausea/Vomiting 4/23 (17.4%) 4 0/24 (0%) 0
    Diarrhea 2/23 (8.7%) 2 1/24 (4.2%) 1
    Constipation 5/23 (21.7%) 5 3/24 (12.5%) 3
    Psychiatric disorders
    Increased energy 0/23 (0%) 0 1/24 (4.2%) 1
    Renal and urinary disorders
    Urinary calcium/Creatinine Ratio 1/23 (4.3%) 1 1/24 (4.2%) 1

    Limitations/Caveats

    Failure to enroll vitamin D deficient patients. The supplements dose were modest. The sample size was small. We may have included too broad a pubertal stage. We did not supplement other micronutrients. We did not include females.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Chadi Calarge, MD
    Organization Baylor College of Medicine
    Phone 832-824-4764
    Email chadi.calarge@bcm.edu
    Responsible Party:
    Chadi A. Calarge, Principal Investigator, University of Iowa
    ClinicalTrials.gov Identifier:
    NCT00799383
    Other Study ID Numbers:
    • 200807730
    • K23MH085005
    First Posted:
    Nov 27, 2008
    Last Update Posted:
    Dec 26, 2017
    Last Verified:
    Nov 1, 2017