Calcium and Vitamin D to Optimize Bone Mass in Boys With Risperidone-induced Hyperprolactinemia
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 |
---|---|---|
|
Phase 3 |
Study Design
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:
|
Placebo Comparator: Placebo Placebo |
Other: Placebo
|
Outcome Measures
Primary Outcome Measures
- 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.
- Total Body Bone Mineral Content [36 weeks]
Outcomes were measured at baseline, 18 weeks, and 36 weeks later.
Secondary Outcome Measures
- Bone Strength Index, mg2/mm4 [36 weeks]
Measured at the 4% radius site.
- Cortical Bone Mineral Density [36 weeks]
This was measured at the 20% radius site.
- Cortical Thickness [36 weeks]
This was measured at the 20% radius site.
- Periosteal Circumference [36 weeks]
This was measured at the 20% radius site.
- Endosteal Circumference [36 weeks]
This was measured at the 20% radius site.
- Polar Section Modulus [36 weeks]
This was measured at the 20% radius site.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Males (age range: 5-17yo; inclusive), in treatment with risperidone for ≥ one year.
-
The participants must have two measurements of prolactin ≥ 18.4 ng/ml, obtained within a week.
-
IQ > 35-40 (≥ Moderate intellectual disability).
-
An adult parent/guardian must be available to provide consent and dispense study medication.
Exclusion Criteria:
-
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.
-
Participants receiving calcium or multivitamins in the previous three months.
-
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).
-
Laboratory values outside the normal range, except for prolactin, unless the deviations were not clinically significant (e.g. TSH < 10 μIU/ml (76)).
-
Inability to cooperate with the BMD measurements.
-
Bilateral wrist or forearm fractures.
-
Eating disorders.
-
Non-compliance with the prescribed psychiatric treatment as reflected by an undetectable combined risperidone and 9-hydroxy risperidone blood concentration.
-
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.- 200807730
- K23MH085005
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
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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
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 |
chadi.calarge@bcm.edu |
- 200807730
- K23MH085005