Trial Outcomes & Findings for Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease (NCT NCT01684722)

NCT ID: NCT01684722

Last Updated: 2022-06-21

Results Overview

GFR estimated from serum creatinine and cystatin C

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 1312 participants
• Primary outcome timeframe: baseline to 5 years
• Results posted on: 2022-06-21

Participant Flow

Participant milestones

Measure	Vitamin D + Fish Oil Placebo Vitamin D and fish oil placebo Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Fish oil placebo: Fish oil placebo	Vitamin D Placebo + Fish Oil Vitamin D placebo and omega-3 fatty acids (fish oil) Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]). Vitamin D placebo: Vitamin D3 placebo	Vitamin D Placebo + Fish Oil Placebo Vitamin D placebo and fish oil placebo Vitamin D placebo: Vitamin D3 placebo Fish oil placebo: Fish oil placebo	Vitamin D + Fish Oil Vitamin D and omega-3 fatty acids (fish oil) Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).
Overall Study STARTED	333	289	320	370
Overall Study COMPLETED	236	212	226	260
Overall Study NOT COMPLETED	97	77	94	110

Reasons for withdrawal

Measure	Vitamin D + Fish Oil Placebo Vitamin D and fish oil placebo Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Fish oil placebo: Fish oil placebo	Vitamin D Placebo + Fish Oil Vitamin D placebo and omega-3 fatty acids (fish oil) Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]). Vitamin D placebo: Vitamin D3 placebo	Vitamin D Placebo + Fish Oil Placebo Vitamin D placebo and fish oil placebo Vitamin D placebo: Vitamin D3 placebo Fish oil placebo: Fish oil placebo	Vitamin D + Fish Oil Vitamin D and omega-3 fatty acids (fish oil) Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).
Overall Study Lost to Follow-up	78	56	75	89
Overall Study Death	19	21	19	21

Baseline Characteristics

Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease

Baseline characteristics by cohort

Measure	Vitamin D + Fish Oil Placebo n=333 Participants Vitamin D and fish oil placebo Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Fish oil placebo: Fish oil placebo	Vitamin D Placebo + Fish Oil n=289 Participants Vitamin D placebo and omega-3 fatty acids (fish oil) Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]). Vitamin D placebo: Vitamin D3 placebo	Vitamin D Placebo + Fish Oil Placebo n=320 Participants Vitamin D placebo and fish oil placebo Vitamin D placebo: Vitamin D3 placebo Fish oil placebo: Fish oil placebo	Vitamin D + Fish Oil n=370 Participants Vitamin D and omega-3 fatty acids (fish oil) Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).	Total n=1312 Participants Total of all reporting groups
Age, Continuous	67.4 years STANDARD_DEVIATION 6.7 • n=5 Participants	68.2 years STANDARD_DEVIATION 6.7 • n=7 Participants	67.5 years STANDARD_DEVIATION 6.9 • n=5 Participants	67.4 years STANDARD_DEVIATION 7.3 • n=4 Participants	67.6 years STANDARD_DEVIATION 6.9 • n=21 Participants
Sex: Female, Male Female	143 Participants n=5 Participants	131 Participants n=7 Participants	151 Participants n=5 Participants	184 Participants n=4 Participants	609 Participants n=21 Participants
Sex: Female, Male Male	190 Participants n=5 Participants	158 Participants n=7 Participants	169 Participants n=5 Participants	186 Participants n=4 Participants	703 Participants n=21 Participants
Race/Ethnicity, Customized Non-Hispanic white	211 Participants n=5 Participants	199 Participants n=7 Participants	207 Participants n=5 Participants	240 Participants n=4 Participants	857 Participants n=21 Participants
Race/Ethnicity, Customized Non-Hispanic black	75 Participants n=5 Participants	59 Participants n=7 Participants	71 Participants n=5 Participants	73 Participants n=4 Participants	278 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic	21 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	20 Participants n=4 Participants	75 Participants n=21 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	8 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants	35 Participants n=21 Participants
Race/Ethnicity, Customized American Indian/Alaska Natuve	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	13 Participants n=21 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	28 Participants n=21 Participants
Race/Ethnicity, Customized Not available	6 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	26 Participants n=21 Participants

PRIMARY outcome

Timeframe: baseline to 5 years

Population: Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.

GFR estimated from serum creatinine and cystatin C

Outcome measures

Measure	Vitamin D n=703 Participants Vitamin D 2000IU daily	Vitamin D Placebo n=609 Participants Matching placebo daily	Fish Oil n=659 Participants Fish oil one capsule daily	Fish Oil Placebo n=653 Participants Matching placebo daily
Change in Estimated Glomerular Filtration Rate	-12.3 mL/min/1.73m2 Interval -13.4 to -11.2	-13.1 mL/min/1.73m2 Interval -14.2 to -11.9	-12.2 mL/min/1.73m2 Interval -13.3 to -11.1	-13.1 mL/min/1.73m2 Interval -14.2 to -12.0

SECONDARY outcome

Timeframe: baseline to 5 years

Population: Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.

Change in urine albumin-creatinine ratio.

Outcome measures

Measure	Vitamin D n=703 Participants Vitamin D 2000IU daily	Vitamin D Placebo n=609 Participants Matching placebo daily	Fish Oil n=659 Participants Fish oil one capsule daily	Fish Oil Placebo n=653 Participants Matching placebo daily
Change in Urine Albumin Excretion	2.97 geometric mean ratio Interval 2.66 to 3.32	3.02 geometric mean ratio Interval 2.7 to 3.38	2.94 geometric mean ratio Interval 2.62 to 3.3	3.05 geometric mean ratio Interval 2.74 to 3.4

SECONDARY outcome

Timeframe: baseline to 5 years

Changes in serum concentrations in CRP

Outcome measures

Measure	Vitamin D n=703 Participants Vitamin D 2000IU daily	Vitamin D Placebo n=609 Participants Matching placebo daily	Fish Oil n=659 Participants Fish oil one capsule daily	Fish Oil Placebo n=653 Participants Matching placebo daily
Change in C-reactive Protein	0.93 mg/L Standard Deviation 2.71	1.03 mg/L Standard Deviation 3.03	0.90 mg/L Standard Deviation 2.82	1.05 mg/L Standard Deviation 2.89

SECONDARY outcome

Timeframe: baseline to 5 years

Changes in serum concentrations in IL-6

Outcome measures

Measure	Vitamin D n=703 Participants Vitamin D 2000IU daily	Vitamin D Placebo n=609 Participants Matching placebo daily	Fish Oil n=659 Participants Fish oil one capsule daily	Fish Oil Placebo n=653 Participants Matching placebo daily
Change in Interleukin-6	1.04 pg/ml Standard Deviation 4.48	1.09 pg/ml Standard Deviation 4.44	1.10 pg/ml Standard Deviation 4.33	1.02 pg/ml Standard Deviation 4.60

SECONDARY outcome

Timeframe: baseline to 5 years

Population: 2x2 factorial design

Changes in serum concentrations in NT-proBNP

Outcome measures

Measure	Vitamin D n=703 Participants Vitamin D 2000IU daily	Vitamin D Placebo n=609 Participants Matching placebo daily	Fish Oil n=659 Participants Fish oil one capsule daily	Fish Oil Placebo n=653 Participants Matching placebo daily
Change in NT-proBNP	1.72 ng/l Standard Deviation 3.24	1.38 ng/l Standard Deviation 3.02	1.56 ng/l Standard Deviation 3.07	1.54 ng/l Standard Deviation 3.24

Adverse Events

Vitamin D + Fish Oil Placebo

Serious events: 45 serious events

Other events: 134 other events

Deaths: 19 deaths

Vitamin D Placebo + Fish Oil

Serious events: 59 serious events

Other events: 135 other events

Deaths: 21 deaths

Vitamin D Placebo + Fish Oil Placebo

Serious events: 45 serious events

Other events: 133 other events

Deaths: 19 deaths

Vitamin D + Fish Oil

Serious events: 44 serious events

Other events: 136 other events

Deaths: 21 deaths

Serious adverse events

Measure	Vitamin D + Fish Oil Placebo n=333 participants at risk Vitamin D and fish oil placebo Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Fish oil placebo: Fish oil placebo	Vitamin D Placebo + Fish Oil n=289 participants at risk Vitamin D placebo and omega-3 fatty acids (fish oil) Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]). Vitamin D placebo: Vitamin D3 placebo	Vitamin D Placebo + Fish Oil Placebo n=320 participants at risk Vitamin D placebo and fish oil placebo Vitamin D placebo: Vitamin D3 placebo Fish oil placebo: Fish oil placebo	Vitamin D + Fish Oil n=370 participants at risk Vitamin D and omega-3 fatty acids (fish oil) Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).
General disorders Malignant cancer	6.3% 21/333 • Up to five years Only monitored safety conditions are reported.	8.3% 24/289 • Up to five years Only monitored safety conditions are reported.	5.3% 17/320 • Up to five years Only monitored safety conditions are reported.	4.6% 17/370 • Up to five years Only monitored safety conditions are reported.
General disorders Cancer death	1.8% 6/333 • Up to five years Only monitored safety conditions are reported.	1.7% 5/289 • Up to five years Only monitored safety conditions are reported.	1.6% 5/320 • Up to five years Only monitored safety conditions are reported.	0.54% 2/370 • Up to five years Only monitored safety conditions are reported.
General disorders Malignant breast cancer	0.60% 2/333 • Up to five years Only monitored safety conditions are reported.	0.35% 1/289 • Up to five years Only monitored safety conditions are reported.	0.94% 3/320 • Up to five years Only monitored safety conditions are reported.	0.54% 2/370 • Up to five years Only monitored safety conditions are reported.
General disorders Malignant prostate cancer	0.90% 3/333 • Up to five years Only monitored safety conditions are reported.	1.4% 4/289 • Up to five years Only monitored safety conditions are reported.	1.2% 4/320 • Up to five years Only monitored safety conditions are reported.	1.1% 4/370 • Up to five years Only monitored safety conditions are reported.
General disorders Malignant colorectal cancer	0.90% 3/333 • Up to five years Only monitored safety conditions are reported.	0.35% 1/289 • Up to five years Only monitored safety conditions are reported.	0.31% 1/320 • Up to five years Only monitored safety conditions are reported.	0.00% 0/370 • Up to five years Only monitored safety conditions are reported.
Cardiac disorders Major CVD events	4.5% 15/333 • Up to five years Only monitored safety conditions are reported.	4.5% 13/289 • Up to five years Only monitored safety conditions are reported.	5.6% 18/320 • Up to five years Only monitored safety conditions are reported.	4.3% 16/370 • Up to five years Only monitored safety conditions are reported.
Cardiac disorders Myocardial infarction	1.8% 6/333 • Up to five years Only monitored safety conditions are reported.	2.1% 6/289 • Up to five years Only monitored safety conditions are reported.	2.5% 8/320 • Up to five years Only monitored safety conditions are reported.	1.6% 6/370 • Up to five years Only monitored safety conditions are reported.
General disorders Stroke	2.4% 8/333 • Up to five years Only monitored safety conditions are reported.	1.7% 5/289 • Up to five years Only monitored safety conditions are reported.	1.2% 4/320 • Up to five years Only monitored safety conditions are reported.	1.6% 6/370 • Up to five years Only monitored safety conditions are reported.
Cardiac disorders Cardiovascular death	1.2% 4/333 • Up to five years Only monitored safety conditions are reported.	1.7% 5/289 • Up to five years Only monitored safety conditions are reported.	2.2% 7/320 • Up to five years Only monitored safety conditions are reported.	1.4% 5/370 • Up to five years Only monitored safety conditions are reported.

Other adverse events

Measure	Vitamin D + Fish Oil Placebo n=333 participants at risk Vitamin D and fish oil placebo Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Fish oil placebo: Fish oil placebo	Vitamin D Placebo + Fish Oil n=289 participants at risk Vitamin D placebo and omega-3 fatty acids (fish oil) Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]). Vitamin D placebo: Vitamin D3 placebo	Vitamin D Placebo + Fish Oil Placebo n=320 participants at risk Vitamin D placebo and fish oil placebo Vitamin D placebo: Vitamin D3 placebo Fish oil placebo: Fish oil placebo	Vitamin D + Fish Oil n=370 participants at risk Vitamin D and omega-3 fatty acids (fish oil) Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Omega-3 fatty acids (fish oil): Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).
Metabolism and nutrition disorders Hypercalcemia	0.90% 3/333 • Number of events 3 • Up to five years Only monitored safety conditions are reported.	2.8% 8/289 • Number of events 8 • Up to five years Only monitored safety conditions are reported.	0.62% 2/320 • Number of events 2 • Up to five years Only monitored safety conditions are reported.	1.6% 6/370 • Number of events 6 • Up to five years Only monitored safety conditions are reported.
Renal and urinary disorders Kidney stones	3.9% 13/333 • Number of events 13 • Up to five years Only monitored safety conditions are reported.	4.2% 12/289 • Number of events 12 • Up to five years Only monitored safety conditions are reported.	4.4% 14/320 • Number of events 14 • Up to five years Only monitored safety conditions are reported.	5.1% 19/370 • Number of events 19 • Up to five years Only monitored safety conditions are reported.
Metabolism and nutrition disorders Parathyroid condition	0.30% 1/333 • Number of events 1 • Up to five years Only monitored safety conditions are reported.	0.69% 2/289 • Number of events 2 • Up to five years Only monitored safety conditions are reported.	0.00% 0/320 • Up to five years Only monitored safety conditions are reported.	0.54% 2/370 • Number of events 2 • Up to five years Only monitored safety conditions are reported.
Gastrointestinal disorders Gastrointestinal bleeding	2.7% 9/333 • Number of events 9 • Up to five years Only monitored safety conditions are reported.	6.2% 18/289 • Number of events 18 • Up to five years Only monitored safety conditions are reported.	2.5% 8/320 • Number of events 8 • Up to five years Only monitored safety conditions are reported.	2.7% 10/370 • Number of events 10 • Up to five years Only monitored safety conditions are reported.
Renal and urinary disorders Blood in urine	9.0% 30/333 • Number of events 30 • Up to five years Only monitored safety conditions are reported.	11.1% 32/289 • Number of events 32 • Up to five years Only monitored safety conditions are reported.	9.1% 29/320 • Number of events 29 • Up to five years Only monitored safety conditions are reported.	6.8% 25/370 • Number of events 25 • Up to five years Only monitored safety conditions are reported.
Blood and lymphatic system disorders Easy bruising	29.4% 98/333 • Number of events 98 • Up to five years Only monitored safety conditions are reported.	31.5% 91/289 • Number of events 91 • Up to five years Only monitored safety conditions are reported.	30.3% 97/320 • Number of events 97 • Up to five years Only monitored safety conditions are reported.	26.8% 99/370 • Number of events 99 • Up to five years Only monitored safety conditions are reported.
Blood and lymphatic system disorders Frequent nosebleeds	3.6% 12/333 • Number of events 12 • Up to five years Only monitored safety conditions are reported.	4.5% 13/289 • Number of events 13 • Up to five years Only monitored safety conditions are reported.	5.3% 17/320 • Number of events 17 • Up to five years Only monitored safety conditions are reported.	3.0% 11/370 • Number of events 11 • Up to five years Only monitored safety conditions are reported.

Additional Information

Ian de Boer, MD, MS

University of Washington

Phone: 2066165403

Email: deboer@u.washington.edu

Results disclosure agreements

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