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Vitamin D/Calcium Polyp Prevention Study

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ClinicalTrials.gov Identifier: NCT00153816
Recruitment Status : Completed
First Posted : September 12, 2005
Results First Posted : October 20, 2015
Last Update Posted : March 15, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Colorectal Cancer
Polyps
Adenomas
Interventions Drug: Calcium Carbonate
Drug: Vitamin D3
Drug: placebo
Enrollment 2813
Recruitment Details Subjects were enrolled between July 2004 and July 2008 at 11 academic medical centers and associated gastroenterology practices in the U.S.
Pre-assignment Details 19,083 subjects were screened and 2,813 were enrolled into a run-in period of 56-84 days. 554 subjects were not randomized: 174 were ineligible due to out of range baseline lab values, 66 were ineligible for other reasons, 211 had <80% tablet adherence, and 103 refused to participate.
Arm/Group Title Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Hide Arm/Group Description

subjects in 2X2 factorial design; randomized to daily placebo

placebo: placebo; two tablets per day

subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Period Title: Overall Study
Started 415 419 420 421 295 289
Completed 383 387 388 390 278 262
Not Completed 32 32 32 31 17 27
Reason Not Completed
Death             6             5             4             6             0             2
Lost to Follow-up             7             8             5             8             7             9
Withdrawal by Subject             9             9             9             4             1             5
Follow-up exam not done             8             7             11             10             8             9
Follow-up exam done, histology missing             2             3             3             3             1             2
Arm/Group Title Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D Total
Hide Arm/Group Description

subjects in 2X2 factorial design; randomized to daily placebo

placebo: placebo; two tablets per day

subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Total of all reporting groups
Overall Number of Baseline Participants 415 419 420 421 295 289 2259
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 415 participants 419 participants 420 participants 421 participants 295 participants 289 participants 2259 participants
58.2  (7.0) 58.7  (7.0) 58.3  (7.0) 58.7  (6.9) 56.7  (6.0) 57.0  (6.6) 58.1  (6.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 419 participants 420 participants 421 participants 295 participants 289 participants 2259 participants
Female
60
  14.5%
63
  15.0%
62
  14.8%
67
  15.9%
295
 100.0%
289
 100.0%
836
  37.0%
Male
355
  85.5%
356
  85.0%
358
  85.2%
354
  84.1%
0
   0.0%
0
   0.0%
1423
  63.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 419 participants 420 participants 421 participants 295 participants 289 participants 2259 participants
Hispanic or Latino
19
   4.6%
23
   5.5%
24
   5.7%
26
   6.2%
28
   9.5%
26
   9.0%
146
   6.5%
Not Hispanic or Latino
395
  95.2%
395
  94.3%
396
  94.3%
394
  93.6%
267
  90.5%
263
  91.0%
2110
  93.4%
Unknown or Not Reported
1
   0.2%
1
   0.2%
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
3
   0.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 415 participants 419 participants 420 participants 421 participants 295 participants 289 participants 2259 participants
American Indian or Alaska Native
4
   1.0%
3
   0.7%
2
   0.5%
2
   0.5%
1
   0.3%
1
   0.3%
13
   0.6%
Asian
8
   1.9%
10
   2.4%
12
   2.9%
6
   1.4%
8
   2.7%
7
   2.4%
51
   2.3%
Native Hawaiian or Other Pacific Islander
2
   0.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.1%
Black or African American
27
   6.5%
33
   7.9%
25
   6.0%
46
  10.9%
28
   9.5%
25
   8.7%
184
   8.1%
White
357
  86.0%
354
  84.5%
364
  86.7%
350
  83.1%
238
  80.7%
237
  82.0%
1900
  84.1%
More than one race
4
   1.0%
4
   1.0%
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.3%
10
   0.4%
Unknown or Not Reported
13
   3.1%
15
   3.6%
16
   3.8%
17
   4.0%
20
   6.8%
18
   6.2%
99
   4.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 415 participants 419 participants 420 participants 421 participants 295 participants 289 participants 2259 participants
Puerto Rico 7 7 7 7 5 4 37
United States 408 412 413 414 290 285 2222
1.Primary Outcome
Title Colorectal Adenomas
Hide Description [Not Specified]
Time Frame 1 to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects are included if they had a follow-up exam at least one year after randomization and had sufficient histology available to ascertain the endpoint.
Arm/Group Title Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Hide Arm/Group Description:

subjects in 2X2 factorial design; randomized to daily placebo

placebo: placebo; two tablets per day

subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Overall Number of Participants Analyzed 380 381 381 381 274 262
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
48.2
(43.0 to 53.3)
44.9
(39.8 to 50.0)
47.0
(41.9 to 52.1)
45.7
(40.6 to 50.8)
32.1
(26.6 to 38.0)
32.4
(26.8 to 38.5)
2.Secondary Outcome
Title Advanced Colorectal Lesions
Hide Description Includes: adenomas >=1 cm, adenomas with high grade dysplasia, adenomas with villous features, or cancer.
Time Frame 1 to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects are included if they had a follow-up exam at least one year after randomization and sufficient histology available to ascertain the endpoint.
Arm/Group Title Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Hide Arm/Group Description:

subjects in 2X2 factorial design; randomized to daily placebo

placebo: placebo; two tablets per day

subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Overall Number of Participants Analyzed 380 386 384 387 276 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
9.2
(6.5 to 12.6)
11.4
(8.4 to 15.0)
10.9
(8.0 to 14.5)
9.6
(6.8 to 12.9)
6.9
(4.2 to 10.5)
7.3
(4.4 to 11.1)
Time Frame Events are included if they occur between randomization and 30 days after the subject exits the treatment phase of the trial, roughly 3 or 5 years after study entry, depending on when their next surveillance colonoscopy is expected.
Adverse Event Reporting Description Every 6 months, subjects were asked to report all hospitalizations and contacts with medical services. All events have been confirmed via medical record review by a study physician.
 
Arm/Group Title Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Hide Arm/Group Description

subjects in 2X2 factorial design; randomized to daily placebo

placebo: placebo; two tablets per day

subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Subjects in 2X2 factorial design; randomized to daily 1000 IU vitamin D3

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Subjects in 2X2 factorial design; randomized to daily 1200 mg as calcium carbonate and 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily placebo

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Women choosing to take daily 1200 mg as calcium carbonate randomized to daily 1000 IU vitamin D3

Calcium Carbonate: 3 gm/daily; 1200 mg elemental calcium/daily; two tablets per day; 600 mg elemental calcium/tablet

Vitamin D3: 1000 IU/daily; two tablets per day; 500 IU per tablet

All-Cause Mortality
Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   84/415 (20.24%)   94/419 (22.43%)   97/420 (23.10%)   80/421 (19.00%)   64/295 (21.69%)   63/289 (21.80%) 
Blood and lymphatic system disorders             
Anemia   2/415 (0.48%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  1/295 (0.34%)  0/289 (0.00%) 
Myelodysplastic syndrome   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Cardiac disorders             
Cardiac arrhythmia   4/415 (0.96%)  3/419 (0.72%)  4/420 (0.95%)  3/421 (0.71%)  1/295 (0.34%)  3/289 (1.04%) 
Cardiac ischemia/myocardial infarction   4/415 (0.96%)  0/419 (0.00%)  6/420 (1.43%)  2/421 (0.48%)  3/295 (1.02%)  1/289 (0.35%) 
Congestive heart failure   3/415 (0.72%)  1/419 (0.24%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  1/289 (0.35%) 
Pericarditis   0/415 (0.00%)  1/419 (0.24%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Valvular heart disease   0/415 (0.00%)  2/419 (0.48%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Ear and labyrinth disorders             
Cochlear implant   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Endocrine disorders             
Thyroid disorder   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Thyroid hyperplasia   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Gastrointestinal disorders             
Abdominal pain   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Appendicitis   0/415 (0.00%)  3/419 (0.72%)  1/420 (0.24%)  2/421 (0.48%)  1/295 (0.34%)  1/289 (0.35%) 
Colostomy take-down   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Constipation   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Diarrhea   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Diverticulitis   2/415 (0.48%)  2/419 (0.48%)  1/420 (0.24%)  1/421 (0.24%)  2/295 (0.68%)  1/289 (0.35%) 
Dysphagia   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Esophagitis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Gastroenteritis   1/415 (0.24%)  0/419 (0.00%)  2/420 (0.48%)  2/421 (0.48%)  1/295 (0.34%)  0/289 (0.00%) 
Gastroesophageal reflux disease   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  2/421 (0.48%)  0/295 (0.00%)  1/289 (0.35%) 
Gastrointestinal hemorrhage   2/415 (0.48%)  1/419 (0.24%)  0/420 (0.00%)  2/421 (0.48%)  1/295 (0.34%)  0/289 (0.00%) 
Hiatal hernia   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Ischemic colitis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Gastrointestinal obstruction   1/415 (0.24%)  2/419 (0.48%)  2/420 (0.48%)  1/421 (0.24%)  1/295 (0.34%)  0/289 (0.00%) 
Pancreatitis   1/415 (0.24%)  2/419 (0.48%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Ulcer   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Volvulus   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
General disorders             
Alcohol intoxication   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Altered mental status   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Altitude sickness   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Chest pain   7/415 (1.69%)  8/419 (1.91%)  8/420 (1.90%)  7/421 (1.66%)  6/295 (2.03%)  4/289 (1.38%) 
Deviated septum   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Epistaxis   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Febrile Illness   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Groin hematoma   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Multiple illnesses   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Septic shock   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Sleep apnea   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Syncope/near syncope   2/415 (0.48%)  2/419 (0.48%)  1/420 (0.24%)  1/421 (0.24%)  1/295 (0.34%)  2/289 (0.69%) 
Toxic shock syndrome   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Traumatic injury   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Hepatobiliary disorders             
Ascites   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Cholecystitis   0/415 (0.00%)  3/419 (0.72%)  4/420 (0.95%)  1/421 (0.24%)  1/295 (0.34%)  2/289 (0.69%) 
Hepatitis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Immune system disorders             
Allergic reaction   2/415 (0.48%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Infections and infestations             
Abscess   0/415 (0.00%)  1/419 (0.24%)  1/420 (0.24%)  1/421 (0.24%)  2/295 (0.68%)  0/289 (0.00%) 
Bacteremia   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Bronchitis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Cellulitis   2/415 (0.48%)  1/419 (0.24%)  0/420 (0.00%)  1/421 (0.24%)  1/295 (0.34%)  0/289 (0.00%) 
Death   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Febrile Illness   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Glottitis   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Infected prosthesis   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Osteomyelitis   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Pneumonia   1/415 (0.24%)  2/419 (0.48%)  1/420 (0.24%)  2/421 (0.48%)  0/295 (0.00%)  2/289 (0.69%) 
Respiratory failure   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Sepsis   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Upper respiratory infection   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Urinary tract infection   1/415 (0.24%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Wound infection   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Injury, poisoning and procedural complications             
Postoperative hematoma   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Sigmoid perforation   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Subdural hematoma   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Unintentional overdose   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Motor vehicle accident   1/415 (0.24%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Metabolism and nutrition disorders             
Electrolyte disturbance   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Hypercalcemia   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Hyperglycemia   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  2/295 (0.68%)  0/289 (0.00%) 
Hyponatremia   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Obesity   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Musculoskeletal and connective tissue disorders             
Chest pain   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Flat feet   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Fracture   6/415 (1.45%)  2/419 (0.48%)  5/420 (1.19%)  2/421 (0.48%)  3/295 (1.02%)  5/289 (1.73%) 
Gout/rheumatoid arthritis   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Hernia   1/415 (0.24%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Joint replacement   5/415 (1.20%)  11/419 (2.63%)  21/420 (5.00%)  13/421 (3.09%)  10/295 (3.39%)  11/289 (3.81%) 
Nerve entrapment   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Tendonitis   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Tenosynovitis   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Traumatic injury   2/415 (0.48%)  0/419 (0.00%)  1/420 (0.24%)  1/421 (0.24%)  1/295 (0.34%)  0/289 (0.00%) 
Ventral hernia   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Back pain/degenerative spinal disorders   5/415 (1.20%)  3/419 (0.72%)  4/420 (0.95%)  9/421 (2.14%)  3/295 (1.02%)  3/289 (1.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Acoustic neuroma   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Benign parotid tumor   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Biliary cancer   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Bladder cancer   0/415 (0.00%)  2/419 (0.48%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Breast cancer/ductal carcinoma in situ  [1]  1/60 (1.67%)  3/63 (4.76%)  0/62 (0.00%)  0/67 (0.00%)  2/295 (0.68%)  2/289 (0.69%) 
Carcinoid   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  1/295 (0.34%)  1/289 (0.35%) 
Central nervous system cancer   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Colorectal cancer   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  1/421 (0.24%)  1/295 (0.34%)  2/289 (0.69%) 
Endometrial cancer/hyperplasia  [1]  2/60 (3.33%)  0/63 (0.00%)  0/62 (0.00%)  1/67 (1.49%)  2/295 (0.68%)  0/289 (0.00%) 
Espohageal cancer   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Head and neck neoplasia   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Kidney cancer   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Lung cancer   1/415 (0.24%)  2/419 (0.48%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Lymphoma/leukemia   3/415 (0.72%)  3/419 (0.72%)  1/420 (0.24%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Melanoma   0/415 (0.00%)  3/419 (0.72%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Myeloma   1/415 (0.24%)  0/419 (0.00%)  1/420 (0.24%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Oncocytoma   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Ovarian cancer  [1]  1/60 (1.67%)  0/63 (0.00%)  0/62 (0.00%)  0/67 (0.00%)  1/295 (0.34%)  2/289 (0.69%) 
Pancreatic cancer   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Peritoneal mesothelioma   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Prostate and bladder cancer  [2]  0/355 (0.00%)  1/356 (0.28%)  0/358 (0.00%)  0/354 (0.00%)  0/0  0/0 
Prostate cancer  [2]  12/355 (3.38%)  12/356 (3.37%)  13/358 (3.63%)  6/354 (1.69%)  0/0  0/0 
Serous ovarian tumor of low malignant potential  [1]  0/60 (0.00%)  1/63 (1.59%)  0/62 (0.00%)  0/67 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Skin basal cell carcinoma   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Thymoma type AB   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Thyroid cancer   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Nervous system disorders             
Amyotrophic lateral sclerosis   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Central nervous system cerebrovascular ischemia   1/415 (0.24%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Cerebral spinal fluid leak   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  1/289 (0.35%) 
Guillain-Barre syndrome   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Hygroma   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Migraine syndrome   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  1/289 (0.35%) 
Multiple sclerosis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Seizure   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  2/295 (0.68%)  0/289 (0.00%) 
Transient global amnesia   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Traumatic injury   0/415 (0.00%)  1/419 (0.24%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
   1/415 (0.24%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Vertigo   0/415 (0.00%)  1/419 (0.24%)  2/420 (0.48%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Vestibular neuritis   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Psychiatric disorders             
Bipolar affective disorder   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Depression   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Steroid psychosis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Renal and urinary disorders             
Cystitis   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Cystocele/rectocele   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  2/289 (0.69%) 
Hematuria   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Urolithiasis   1/415 (0.24%)  3/419 (0.72%)  1/420 (0.24%)  2/421 (0.48%)  1/295 (0.34%)  1/289 (0.35%) 
Renal failure   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Reproductive system and breast disorders             
Benign prostatic hyperplasia  [2]  3/355 (0.85%)  5/356 (1.40%)  4/358 (1.12%)  1/354 (0.28%)  0/0  0/0 
Breast surgery  [1]  0/60 (0.00%)  0/63 (0.00%)  0/62 (0.00%)  0/67 (0.00%)  3/295 (1.02%)  0/289 (0.00%) 
Corpus luteum cyst  [1]  0/60 (0.00%)  0/63 (0.00%)  0/62 (0.00%)  0/67 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Fibroids  [1]  2/60 (3.33%)  0/63 (0.00%)  0/62 (0.00%)  0/67 (0.00%)  1/295 (0.34%)  1/289 (0.35%) 
Pubovaginal sling  [1]  0/60 (0.00%)  0/63 (0.00%)  0/62 (0.00%)  0/67 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Uterine prolapse  [1]  0/60 (0.00%)  0/63 (0.00%)  0/62 (0.00%)  1/67 (1.49%)  1/295 (0.34%)  1/289 (0.35%) 
Vaginal bleeding  [1]  0/60 (0.00%)  1/63 (1.59%)  0/62 (0.00%)  0/67 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Vaginal prolapse  [1]  0/60 (0.00%)  0/63 (0.00%)  1/62 (1.61%)  0/67 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Asthma   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Chronic obstructive pulmonary disease   1/415 (0.24%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  3/289 (1.04%) 
Malignant pleural effusion   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Pneumonitis   0/415 (0.00%)  2/419 (0.48%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Pulmonary fibrosis   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Traumatic injury   2/415 (0.48%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Skin and subcutaneous tissue disorders             
Cosmetic surgery   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Vascular disorders             
Aneurysm   0/415 (0.00%)  0/419 (0.00%)  1/420 (0.24%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Cerebrovascular ischemia   1/415 (0.24%)  0/419 (0.00%)  3/420 (0.71%)  3/421 (0.71%)  3/295 (1.02%)  4/289 (1.38%) 
Hypotension   0/415 (0.00%)  1/419 (0.24%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Phlebitis   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  1/295 (0.34%)  0/289 (0.00%) 
Revascularization   3/415 (0.72%)  7/419 (1.67%)  3/420 (0.71%)  6/421 (1.43%)  1/295 (0.34%)  4/289 (1.38%) 
Subdural hematoma   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  1/289 (0.35%) 
Sudden death   0/415 (0.00%)  0/419 (0.00%)  0/420 (0.00%)  1/421 (0.24%)  0/295 (0.00%)  0/289 (0.00%) 
Traumatic injury   1/415 (0.24%)  0/419 (0.00%)  0/420 (0.00%)  0/421 (0.00%)  0/295 (0.00%)  0/289 (0.00%) 
Venous thromboembolism   1/415 (0.24%)  2/419 (0.48%)  6/420 (1.43%)  1/421 (0.24%)  1/295 (0.34%)  1/289 (0.35%) 
Indicates events were collected by systematic assessment
[1]
Only women are considered at risk
[2]
Only men are considered at risk
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Full Factorial Placebo Full Factorial Calcium Full Factorial Vitamin D Full Factorial Calcium Plus Vitamin D Two Arm Placebo Two Arm Vitamin D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   46/415 (11.08%)   45/419 (10.74%)   47/420 (11.19%)   61/421 (14.49%)   53/295 (17.97%)   40/289 (13.84%) 
Musculoskeletal and connective tissue disorders             
Fracture   15/415 (3.61%)  12/419 (2.86%)  15/420 (3.57%)  21/421 (4.99%)  22/295 (7.46%)  7/289 (2.42%) 
Osteopenia   5/415 (1.20%)  8/419 (1.91%)  6/420 (1.43%)  7/421 (1.66%)  17/295 (5.76%)  16/289 (5.54%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Non-melanoma skin cancer   20/415 (4.82%)  26/419 (6.21%)  22/420 (5.24%)  28/421 (6.65%)  11/295 (3.73%)  11/289 (3.81%) 
Renal and urinary disorders             
Hypercreatinemia  [1]  21/407 (5.16%)  29/412 (7.04%)  19/415 (4.58%)  29/413 (7.02%)  17/294 (5.78%)  9/287 (3.14%) 
Indicates events were collected by systematic assessment
[1]
Hypercreatinemia is a value on a safety blood draw above normal for subjects whose baseline creatinine was normal. Only subjects who had at least one safety blood draw are included.
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
Layout table for Results Point of Contact information
Name/Title: Leila A. Mott, Statistical Analyst
Organization: Geisel School of Medicine at Dartmouth
Phone: 603-650-3447
EMail: Leila.A.Mott@Dartmouth.EDU
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00153816     History of Changes
Other Study ID Numbers: 5R01CA098286-03 ( U.S. NIH Grant/Contract )
5R01CA098286-10 ( U.S. NIH Grant/Contract )
First Submitted: September 7, 2005
First Posted: September 12, 2005
Results First Submitted: September 21, 2015
Results First Posted: October 20, 2015
Last Update Posted: March 15, 2017