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

Counteracting Risperidone-Induced Hyperprolactinemia in Youths

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.

Study Overview

• Status: Completed
• Conditions: Risperidone-induced Hyperprolactinemia
• Intervention / Treatment: Other: Placebo; Drug: Calcium and Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trabecular Bone Mineral Density in the Ultradistal Radius	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.	36 weeks
Total Body Bone Mineral Content	Outcomes were measured at baseline, 18 weeks, and 36 weeks later.	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Strength Index, mg2/mm4	Measured at the 4% radius site.	36 weeks
Cortical Bone Mineral Density	This was measured at the 20% radius site.	36 weeks
Cortical Thickness	This was measured at the 20% radius site.	36 weeks
Periosteal Circumference	This was measured at the 20% radius site.	36 weeks
Endosteal Circumference	This was measured at the 20% radius site.	36 weeks
Polar Section Modulus	This was measured at the 20% radius site.	36 weeks

Collaborators and Investigators

• Sponsor: Chadi A. Calarge
• Collaborators: National Institute of Mental Health (NIMH); Children's Miracle Network
• Investigators: Principal Investigator: Chadi Calarge, M.D., University of Iowa

Publications and helpful links

General Publications

• Calarge CA, Mills JA, Ziegler EE, Schlechte JA. Calcium and Vitamin D Supplementation in Boys with Risperidone-Induced Hyperprolactinemia: A Randomized, Placebo-Controlled Pilot Study. J Child Adolesc Psychopharmacol. 2018 Mar;28(2):145-150. doi: 10.1089/cap.2017.0104. Epub 2017 Nov 7.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: November 25, 2008
• First Submitted That Met QC Criteria: November 26, 2008
• First Posted (Estimate): November 27, 2008

Study Record Updates

• Last Update Posted (Actual): December 26, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: children; prevention; Risperidone; adolescents; antipsychotics; vitamin D; calcium; hyperprolactinemia; Risperidone-induced hyperprolactinemia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Hyperprolactinemia; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium
• Other Study ID Numbers: 200807730; K23MH085005 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No