Calcium Absorption in Patients With Rothmund-Thomson Syndrome

• ClinicalTrials.gov Identifier: NCT01304407
• Recruitment Status: Completed
• First Posted: February 25, 2011
• Results First Posted: July 8, 2020
• Last Update Posted: July 23, 2020
• Sponsor: Baylor College of Medicine
• Collaborators: United States Department of Agriculture (USDA); National Institutes of Health (NIH); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Gillson-Longenbaugh Foundation
• Information provided by (Responsible Party): Steve Abrams, MD, Baylor College of Medicine

Study Description

Brief Summary:

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Because cure rates for osteosarcoma have remained stagnant for the past several decades despite numerous trials of chemotherapy agents, novel therapies based on the understanding of the molecular pathogenesis of osteosarcoma are needed. Rothmund-Thomson Syndrome (RTS) is a genetic disorder affecting many parts of the body and resulting in major skeletal abnormalities. This disease also has the propensity to increase the risk of developing cancer, particularly osteosarcoma. Two-thirds of RTS patients have a high risk of developing osteosarcoma. Therefore, it is important to understand the impact of RTS on the skeletal phenotype (as measured by bone density) in order to develop effective therapies to battle osteosarcoma.

Condition or disease	Intervention/treatment	Phase
Rothmund-Thomson Syndrome	Other: Calcium stable isotope	Not Applicable

Detailed Description:

This is an evaluation of bone calcium deposition in patients with Rothmund-Thomson Syndrome (RTS).

This study includes one study visit during which subjects will be admitted to the inpatient unit in the Pediatric GCRC at TCH where they will undergo comprehensive clinical evaluations by a team of physicians familiar with RTS as well as bone-specific studies divided into four parts. Procedures for this study may be combined with procedures for H-9106, another protocol for patients with RTS by Dr. Wang.

Subjects will arrive at the GCRC at TCH after an overnight fast. Per TCH pain management protocols, numbing creams and sprays will be offered to the subject prior to the blood draw. Tylenol per TCH pain protocol is allowed. All food and beverages consumed at the GCRC will be pre-arranged by the study dietitian and weighed by the GCRC nutrition staff. Additional food is not allowed unless approved by the study dietitian.

Subjects will be asked to provide a 3-day written dietary history as well as food preferences for the GCRC study day. For the first meal of the study day, subjects will consume 180 mL of low-fat milk or orange juice to which 20 micrograms of 46Ca will have been added. (If milk is used as the vehicle for the isotope, the 46Ca will be added 18-24 hours in advance.)

Immediately after breakfast, subjects will receive 5 mg of 42Ca intravenously over 2-3 minutes. The beginning of this infusion will serve as Time 0. After the infusion is complete, the catheter hub will be changed in preparation for the subsequent blood draws. Samples for calcium isotope ratio measurement (0.5 ml of whole blood) will be obtained at 6, 12, 20, 40, 120, 180, 240, and 480 minutes after the infusion.

GCRC will provide weighed diets for the study day as directed by the study dietitian. Each meal should contain approximately 300 mg of calcium and each snack should provide negligible calcium. A complete 24-hour urine collection in 8 hour aliquots will be performed while at the GCRC starting with the first void after the isotopes are given.

After completion of this 24 hour period, the subjects will be discharged. They will continue to collect all of their urine in 8 hour aliquots for an additional 24 hours and then will collect three spot urine samples each day for the next 6 days. These samples will then be mailed to the CNRC research laboratory of Dr. Steven Abrams where they will be analyzed for isotope ratios by mass spectrometry analysis.

Upon discharge, subjects will receive a food scale and instruction sheets on recording their dietary intake for the next 3 days (i.e., weighed food record). While inpatient, the study dietitian will instruct the family on the guidelines for recording this intake. After the 3 days, the food scale and records will be returned to the CNRC for analysis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Evaluation of Calcium Absorption in Patients With Rothmund-Thomson Syndrome
• Study Start Date: March 2011
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: February 2017

Arms and Interventions

Arm	Intervention/treatment
RTS Subjects, Calcium Isotope; Subjects consume breakfast and 180 ml of calcium-fortified orange juice to which 20 mg of 46Ca stable isotope was added. Immediately after breakfast, subjects receive 5 mg of 42Ca intravenously.	Other: Calcium stable isotope; Subjects consume breakfast and 180 ml of calcium-fortified orange juice to which 20 mg of 46Ca stable isotope was added. Immediately after breakfast, subjects receive 5 mg of 42Ca intravenously.

Outcome Measures

Primary Outcome Measures :

1. Bone Density (Low Areal Bone Mineral Density (aBMD)) [ Time Frame: 8 days ]
   Individuals had low areal bone mineral density (aBMD) assessed by DXA using a Hologic Delphi-A instrument (Bedford, MA) at the Body Composition Laboratory of the Children's Nutrition Research Center, Houston, TX. Scans were performed of the whole body, lumbar spine, and proximal femur. Bone mineral content (BMC), bone area, and BMD were measured using Hologic Discovery V12.1 analysis software. For adult subjects, BMD Z-scores of the whole body, lumbar spine, left total hip, and left femoral neck were calculated using the Hologic Reference Database. Validated age- and sex-matched control data from the pediatric population generated by the Body Composition Laboratory of the Children's Nutrition Research Center, Houston, TX were used to calculate the Z-scores for pediatric subjects as previously published.

Eligibility Criteria

• Ages Eligible for Study: 4 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients at least four years of age who have been diagnosed clinically with RTS by a physician.

Exclusion Criteria:

• Any person who does not meet the inclusion criteria.

Contacts and Locations

Locations

United States, Texas

Baylor College of Medicine / Texas Children's Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Baylor College of Medicine

United States Department of Agriculture (USDA)

National Institutes of Health (NIH)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Gillson-Longenbaugh Foundation

Investigators

• Principal Investigator: Lisa Wang, MD; Baylor College of Medicine

More Information

• Responsible Party: Steve Abrams, MD, Professor, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT01304407
• Other Study ID Numbers: H-27088; R01AR059063 ( U.S. NIH Grant/Contract )
• First Posted: February 25, 2011
• Results First Posted: July 8, 2020
• Last Update Posted: July 23, 2020
• Last Verified: July 2020

Keywords provided by Steve Abrams, MD, Baylor College of Medicine:

Rothmund-Thomson Syndrome; Calcium absorption; Bone density

Additional relevant MeSH terms:

Rothmund-Thomson Syndrome; Syndrome; Disease; Pathologic Processes; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Skin Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs