Trial Outcomes & Findings for A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors (NCT NCT00186901)

NCT ID: NCT00186901

Last Updated: 2017-05-10

Results Overview

The effect of taking calcium and vitamin D supplements was measured using Quantitative Computed Tomography (QCT) to calculate a QTC Z score. A standardized Z-score was calculated to indicate the difference between the patient's Bone Mineral Density (BMD) and the mean value for age and gender-appropriate controls. Z-scores from 0 to +2 are considered normal, above +2 are considered to be elevated, from 0 to -1 are considered to represent a mild BMD deficit, between -1 and -2 are considered to represent moderate deficits, and below -2 are considered to represent severe deficits.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 429 participants
• Primary outcome timeframe: Baseline, 12 months, 24 months, and at 36 months or study end
• Results posted on: 2017-05-10

Participant Flow

429 patients were recruited at St. Jude Children's Research Hospital between August 7, 2000 and July 27, 2006. 4 patients were found to be ineligible and 1 patient was taken off study per the PI's request. 424 patients were available at baseline.

424 total patients were enrolled on the study. 149 patients were ineligible for randomization. 275 patients were identified with Bone Mineral Density (BMD) Z-scores > 0 and thus were eligible for intervention and were randomized to receive either Calcium and Vitamin D supplementation or placebo.

Participant milestones

Measure	Placebo Group Nutritional counseling + placebo	Supplement Group Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period	Patients Ineligible for Randomization 424 patients were enrolled into the study, 149 were ineligible for randomization.
Overall Study STARTED	134	141	149
Overall Study Baseline	134	141	0
Overall Study 12 Month Follow-up	117	122	0
Overall Study 24 Month Follow-up	106	107	0
Overall Study COMPLETED	85	96	0
Overall Study NOT COMPLETED	49	45	149

Reasons for withdrawal

Measure	Placebo Group Nutritional counseling + placebo	Supplement Group Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period	Patients Ineligible for Randomization 424 patients were enrolled into the study, 149 were ineligible for randomization.
Overall Study Pregnancy	6	3	0
Overall Study Lost to Follow-up	6	3	0
Overall Study Bone Mineral Density dropped > 5%	9	7	0
Overall Study ALL relapse or second malignancy	1	2	0
Overall Study Withdrawal by Subject	4	5	0
Overall Study Open label	3	2	0
Overall Study Limited adherence to study requirements	20	23	0
Overall Study Bone Mineral Density > 0	0	0	149

Baseline Characteristics

A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors

Baseline characteristics by cohort

Measure	Placebo Group n=134 Participants Nutritional counseling + placebo	Supplement Group n=141 Participants Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period	Patients Ineligible for Randomization n=149 Participants 424 patients were enrolled into the study, 149 were ineligible for randomization.	Total n=424 Participants Total of all reporting groups
Age, Continuous	17.9 years STANDARD_DEVIATION 5.6 • n=5 Participants	17.6 years STANDARD_DEVIATION 6.3 • n=7 Participants	19.2 years STANDARD_DEVIATION 6.6 • n=5 Participants	17.8 years STANDARD_DEVIATION 5.9 • n=4 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	63 Participants n=7 Participants	87 Participants n=5 Participants	206 Participants n=4 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	78 Participants n=7 Participants	62 Participants n=5 Participants	218 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 12 months, 24 months, and at 36 months or study end

Population: Of the 275 pts identified with BMD z-scores \< 0, 134 were randomized to the placebo group and 141 to the supplement group. Bone Mineral Density QCT Z-scores were calculated at baseline, 12 months, 24 months, and at 36 months or study end.

The effect of taking calcium and vitamin D supplements was measured using Quantitative Computed Tomography (QCT) to calculate a QTC Z score. A standardized Z-score was calculated to indicate the difference between the patient's Bone Mineral Density (BMD) and the mean value for age and gender-appropriate controls. Z-scores from 0 to +2 are considered normal, above +2 are considered to be elevated, from 0 to -1 are considered to represent a mild BMD deficit, between -1 and -2 are considered to represent moderate deficits, and below -2 are considered to represent severe deficits.

Outcome measures

Measure	Placebo n=134 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=141 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years 113 patients greater than 22 years of age were eligible for the study
Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD) Baseline	-0.95 Z-Score Interval -3.09 to -0.05	-0.97 Z-Score Interval -3.94 to -0.04	—	—
Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD) 12 Months	-0.87 Z-Score Interval -3.23 to 0.85	-1.04 Z-Score Interval -4.32 to 0.58	—	—
Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD) 24 Months	-0.72 Z-Score Interval -2.61 to 0.91	-0.76 Z-Score Interval -3.75 to 1.23	—	—
Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD) 36 Months (study end)	-0.56 Z-Score Interval -2.96 to 1.36	-0.61 Z-Score Interval -4.23 to 2.02	—	—

PRIMARY outcome

Timeframe: Baseline

Population: Baseline participants were assessed to determine whether gender was a pre-disposing factor for bone mineral density.

Using bone mineral density Z-score, assess relationship between predisposing factors (gender) and bone mineral density; a negative value indicates a deficit in bone mineral density.

Outcome measures

Measure	Placebo n=218 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=206 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years 113 patients greater than 22 years of age were eligible for the study
Bone Mineral Density in Male and Female ALL Survivors	-0.62 Z-score Standard Error 1.18	-0.3 Z-score Standard Error 1.18	—	—

PRIMARY outcome

Timeframe: Baseline

Population: Assess baseline participants to determine whether race contributed to bone mineral density.

Using bone mineral density Z-score, assess relationship between predisposing factors (race) and bone mineral density; a negative value indicates a deficit in bone mineral density.

Outcome measures

Measure	Placebo n=365 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=59 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years 113 patients greater than 22 years of age were eligible for the study
Bone Mineral Density by Race of ALL Survivors	-0.54 Z-score Standard Error 1.14	0.15 Z-score Standard Error 1.56	—	—

PRIMARY outcome

Timeframe: Baseline

Population: Assess baseline participants to determine whether age was a contributing factor in bone mineral density.

Using bone mineral density Z-score, assess relationship between predisposing factors (age groups) and bone mineral density; a negative value indicates a deficit in bone mineral density.

Outcome measures

Measure	Placebo n=98 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=139 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=74 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years n=113 Participants 113 patients greater than 22 years of age were eligible for the study
Bone Mineral Density by Age Group of ALL Survivors	-0.6 Z-score Standard Error 1.1	-0.54 Z-score Standard Error 1.21	-0.59 Z-score Standard Error 1.2	-0.25 Z-score Standard Error 1.29

SECONDARY outcome

Timeframe: Baseline

Population: 275 patients were assessed at baseline and received a QCT Scan. 121 patients were also assessed using the DEXA Scan. Comparison of the two methods used 121 paired studies to arrive at a correlation coefficient.

To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 121 patients at baseline were assessed by both method the QCT and DXA methods to assess Bone Mineral Density.

Outcome measures

Measure	Placebo n=134 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=60 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=141 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years n=61 Participants 113 patients greater than 22 years of age were eligible for the study
Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	-1.06 Z-score Standard Deviation 0.70 • Interval 0.25 to 0.55	-1.30 Z-score Standard Deviation 1.21	-1.09 Z-score Standard Deviation 0.74	-1.18 Z-score Standard Deviation 1.02

SECONDARY outcome

Timeframe: 12 months

Population: 218 patients were assessed at the 12 months interval and received a QCT Scan. 94 patients were also assessed using the DXA Scan. Comparison of the two methods used 94 paired studies to arrive at a correlation.

To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 218 patients were assessed at 12 months for QCT. 94 were evaluated using DXA. 94 patients received both scans.

Outcome measures

Measure	Placebo n=109 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=47 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=109 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years n=47 Participants 113 patients greater than 22 years of age were eligible for the study
Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	-1.02 Z-score Standard Deviation 0.87 • Interval 0.38 to 0.67	-1.20 Z-score Standard Deviation 1.36	-1.04 Z-score Standard Deviation 0.89	-0.79 Z-score Standard Deviation 0.93

SECONDARY outcome

Timeframe: 24 months

Population: 188 patients were assessed at the 24 months interval and received a QCT Scan. 90 patients were also assessed using the DXA Scan. Comparison of the two methods used 90 paired studies to arrive at a correlation.

To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 188 patients were assessed at 24 months by the QCT method and 90 were evaluated using the DXA methods to assess Bone Mineral Density. 90 patients received both scans.

Outcome measures

Measure	Placebo n=91 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=39 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=97 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years n=51 Participants 113 patients greater than 22 years of age were eligible for the study
Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	-0.75 Z-score Standard Deviation 0.82 • Interval 0.36 to 0.66	-0.77 Z-score Standard Deviation 1.31	-0.84 Z-score Standard Deviation 0.86	-0.60 Z-score Standard Deviation 1.07

SECONDARY outcome

Timeframe: 36 months

Population: 180 patients were assessed at the 36 months interval and received a QCT Scan. 89 patients were also assessed using the DEXA Scan. Comparison of the two methods produced 89 paired studies to arrive at a correlation.

To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 180 patients were assessed at 36 months by the QCT method and 89 were evaluated using the DXA methods to assess Bone Mineral Density. 89 patients received both scans.

Outcome measures

Measure	Placebo n=84 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=36 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=96 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years n=53 Participants 113 patients greater than 22 years of age were eligible for the study
Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.	-0.54 Z-score Standard Deviation 0.86 • Interval 0.3 to 0.63	-0.63 Z-score Standard Deviation 1.14	-0.71 Z-score Standard Deviation 0.98	-0.63 Z-score Standard Deviation 1.00

SECONDARY outcome

Timeframe: At enrollment

Population: Of the 424 patients screened, 417 participants consented for genetic testing. Of the 417 patients screened for the Apa 1 vitamin D receptor, only 68 had the AA genotype, 104 had the Aa genotype, and 49 had the aa genotype.

The Apa1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood

Outcome measures

Measure	Placebo n=68 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=104 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=49 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years 113 patients greater than 22 years of age were eligible for the study
Mean QCT Z-Score by Apa1 Vitamin D Receptor Genotype	-0.56 QCT Z-Score Standard Deviation 1.27	-0.44 QCT Z-Score Standard Deviation 1.28	-0.57 QCT Z-Score Standard Deviation 1.13	—

SECONDARY outcome

Timeframe: At enrollment

Population: Of the 424 patients screened, 417 participants consented for genetic testing. Of the 417 patients screened for the Bsm 1 vitamin D receptor, only 41 had the BB genotype, 65 had the Bb genotype, and 77 had the bb genotype.

The Bsm1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood

Outcome measures

Measure	Placebo n=41 Participants Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.	Supplement n=65 Participants CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.	18 to 22 Years n=77 Participants 74 patients between the ages of 18 and 22 were eligible for the study	Above 22 Years 113 patients greater than 22 years of age were eligible for the study
Mean QCT Z-Score by Bsm 1 Vitamin D Receptor Genotype	-0.5 QCT Z-Score Standard Deviation 1.2	-0.17 QCT Z-Score Standard Deviation 1.25	-0.17 QCT Z-Score Standard Deviation 1.24	—

Adverse Events

Placebo Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Supplement Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Patients Ineligible for Randomization

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Sue Kaste, DO

St. Jude Children's Research Hospital

Phone: 866-278-5833

Email: referralinfo@stjude.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place