CaDDM: Vitamin D and Calcium Homeostasis for Prevention of Type 2 Diabetes

• Sponsor: Tufts Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00436475
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 92
• Location: 1
• Arms: 4
• Duration (Months): 26
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The purpose of the randomized trial is to quantify the effect of vitamin D and calcium supplementation on beta-cell function, insulin sensitivity, glucose tolerance and systemic inflammation and other cardiometabolic outcomes in ambulatory adults at high risk for type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Glucose Intolerance; Type 2 Diabetes Mellitus; Metabolic Syndrome	Drug: Vitamin D3 2,000 IU orally once daily; Drug: Calcium Carbonate 400 mg orally twice daily; Drug: Vitamin D3-Placebo; Drug: Calcium-Placebo	Phase 1/Phase 2

Detailed Description

There is animal and human observational evidence to suggest that vitamin D and calcium are important in modifying t2DM risk but there are critical gaps in our knowledge about the clinical magnitude of the association with t2DM and potential mechanisms in humans. We are conducting a randomized trial to quantify the effect of vitamin D and calcium supplementation on beta-cell function, insulin sensitivity, glucose tolerance and systemic inflammation and other cardiometabolic outcomes in ambulatory adults at high risk for t2DM. We anticipate that the research proposed in this application is significant because it will provide the basis for defining feasible nutritional interventions that promotes prevention of t2DM. Based on the results of the proposed studies and future work in this area, vitamin D and calcium supplementation can assume an important role in the treatment of t2DM and in the prevention of the disease in the 41 million Americans who are at risk of developing t2DM.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Vitamin D and Calcium Homeostasis for Prevention of Type 2 Diabetes
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily	Drug: Vitamin D3 2,000 IU orally once daily; Vitamin D3 2,000 IU orally once daily; Drug: Calcium Carbonate 400 mg orally twice daily; Calcium Carbonate 400 mg orally twice daily
Other: 2 Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily	Drug: Vitamin D3 2,000 IU orally once daily; Vitamin D3 2,000 IU orally once daily; Drug: Calcium-Placebo; Calcium-Placebo
Other: 3 Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily	Drug: Calcium Carbonate 400 mg orally twice daily; Calcium Carbonate 400 mg orally twice daily; Drug: Vitamin D3-Placebo; Vitamin D3-Placebo
Other: 4 Vitamin D3-Placebo plus Calcium-Placebo	Drug: Vitamin D3-Placebo; Vitamin D3-Placebo; Drug: Calcium-Placebo; Calcium-Placebo

Outcome Measures

Primary Outcome Measures

1. Chang in Disposition Index, a Measure of Beta Cell Function [baseline and 4 months]

   Range is 0 to infinity Lower is better.

Secondary Outcome Measures

1. Change in Hemoglobin A1c [Baseline to 4 months]

   This outcome measures change in Hemoglobin A1c, a measure of glycemia

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ethnicity: all ethnic groups

• Gender: men and women

• Age

1. Lower age limit: 40 years inclusive

2. Upper age limit: NONE

• BMI

1. Lower BMI limit: 25 inclusive

2. Upper BMI limit: 40 inclusive

• Glucose Intolerance / Mild Diabetes defined as

1. Fasting glucose ≥100 mg/dl OR

2. 2-hr glucose after OGTT ≥140 mg/dl OR

3. 5.8 ≤ Hemoglobin A1c ≤ 7

Major Exclusion Criteria:

• Diabetes requiring pharmacotherapy

• Smoking

• Hyperparathyroidism

• Hypercalcemia (Calcium > 10.5 mg/dl)

• Kidney stone

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts-New England Medical Center	Boston	Massachusetts	United States	02111

Sponsors and Collaborators

• Tufts Medical Center
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Anastassios G Pittas, MD MS, Tufts Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

• Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006 Mar;29(3):650-6.
• Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007 Apr;30(4):980-6. Epub 2007 Feb 2.
• Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review.

• Responsible Party: Tufts Medical Center
• ClinicalTrials.gov Identifier: NCT00436475
• Other Study ID Numbers: DK76092 (completed); R01DK076092; DK76092
• First Posted: Feb 19, 2007
• Last Update Posted: Jul 30, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Tufts Medical Center: Glucose intolerance; Type 2 diabetes mellitus; Metabolic syndrome
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Syndrome; Glucose Intolerance; Calcium, Dietary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Calcium Carbonate; Calcium

Study Results

Participant Flow

Arm/Group Title	Vitamin D-Calcium	Vitamin D Only	Calcium Only	Placebo-Placebo
Arm/Group Description	Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily	Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily	Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily	Vitamin D3-Placebo plus Calcium-Placebo
Period Title: Overall Study
STARTED	23	23	22	24
COMPLETED	23	22	21	22
NOT COMPLETED	0	1	1	2

Baseline Characteristics

Arm/Group Title	Vitamin D-Calcium	Vitamin D Only	Calcium Only	Placebo-Placebo	Total
Arm/Group Description	Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily	Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily	Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily	Vitamin D3-Placebo plus Calcium-Placebo	Total of all reporting groups
Overall Participants	23	23	22	24	92
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	23 100%	22 100%	24 100%	92 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (2)	57 (2)	57 (2)	59 (2)	57 (1)
Sex: Female, Male (Count of Participants)
Female	12 52.2%	12 52.2%	10 45.5%	13 54.2%	47 51.1%
Male	11 47.8%	11 47.8%	12 54.5%	11 45.8%	45 48.9%
Region of Enrollment (Count of Participants)
United States	23 100%	23 100%	22 100%	24 100%	92 100%

Outcome Measures

1. Primary Outcome

Title	Chang in Disposition Index, a Measure of Beta Cell Function
Description	Range is 0 to infinity Lower is better.
Time Frame	baseline and 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D-Calcium	Vitamin D Only	Calcium Only	Placebo-Placebo
Arm/Group Description	Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily	Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily	Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily	Vitamin D3-Placebo plus Calcium-Placebo
Measure Participants	23	23	21	22
Mean (Standard Error) [units on a scale]	287 (170)	314 (183)	-122 (177)	-129 (174)

2. Secondary Outcome

Title	Change in Hemoglobin A1c
Description	This outcome measures change in Hemoglobin A1c, a measure of glycemia
Time Frame	Baseline to 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D-Calcium	Vitamin D Only	Calcium Only	Placebo-Placebo
Arm/Group Description	Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily	Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily	Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily	Vitamin D3-Placebo plus Calcium-Placebo
Measure Participants	23	23	22	24
Mean (Standard Error) [% of hemoglobin]	0.05 (0.05)	0.08 (0.05)	0.09 (0.05)	0.18 (0.04)

Adverse Events

Arm/Group Title	Vitamin D-Calcium		Vitamin D Only		Calcium Only		Placebo-Placebo
Arm/Group Description	Vitamin D3 2,000 IU daily plus Calcium Carbonate 400 mg twice daily		Vitamin D3 2,000 IU daily plus Calcium-Placebo twice daily		Vitamin D3-Placebo plus Calcium Carbonate 400 mg twice daily		Vitamin D3-Placebo plus Calcium-Placebo
All Cause Mortality
	Vitamin D-Calcium		Vitamin D Only		Calcium Only		Placebo-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitamin D-Calcium		Vitamin D Only		Calcium Only		Placebo-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		0/23 (0%)		1/22 (4.5%)		0/24 (0%)
General disorders
Hospitalization	1/23 (4.3%)		0/23 (0%)		1/22 (4.5%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D-Calcium		Vitamin D Only		Calcium Only		Placebo-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/23 (26.1%)		4/23 (17.4%)		5/22 (22.7%)		4/24 (16.7%)
Eye disorders
Eye irritation	0/23 (0%)		1/23 (4.3%)		0/22 (0%)		0/24 (0%)
General disorders
Pain	1/23 (4.3%)		0/23 (0%)		0/22 (0%)		0/24 (0%)
Injury	1/23 (4.3%)		1/23 (4.3%)		0/22 (0%)		0/24 (0%)
Other	0/23 (0%)		0/23 (0%)		2/22 (9.1%)		2/24 (8.3%)
Musculoskeletal and connective tissue disorders
Joint pain	3/23 (13%)		2/23 (8.7%)		1/22 (4.5%)		0/24 (0%)
Renal and urinary disorders
UTI	0/23 (0%)		0/23 (0%)		0/22 (0%)		0/24 (0%)
Respiratory, thoracic and mediastinal disorders
URI	1/23 (4.3%)		0/23 (0%)		2/22 (9.1%)		2/24 (8.3%)

Limitations/Caveats

Fewer participants than anticipated were enrolled because of reduction in budget.

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.