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The VALIDATE-D Study (VALIDATE-D)

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ClinicalTrials.gov Identifier: NCT01635062
Recruitment Status : Completed
First Posted : July 6, 2012
Results First Posted : April 11, 2017
Last Update Posted : April 11, 2017
Sponsor:
Information provided by (Responsible Party):
Anand Vaidya, Brigham and Women's Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Type 2 Diabetes
Obesity
Interventions Drug: Calcitriol
Drug: Placebo
Enrollment 41
Recruitment Details

Subjects were recruited from the local Boston community

A total of 41 participants were consented to participate. Subsequently, 13 were found ineligible, 5 withdrew participation, 3 were lost-to follow-up, and 2 were withdrawn for non-compliance with the washout. Therefore, 18 were randomized.

Pre-assignment Details

An anti-hypertensive medication washout was conducted to minimize confounding of the renin-angiotensin system.

ACE inhibitors, angiotensin-receptor blockers, and mineralocorticoid receptor antagonists, beta blockers, diuretics, and calcium-channel blockers were withdrawn for 2 weeks to 2 months prior to randomization.

Arm/Group Title Calcitriol Placebo
Hide Arm/Group Description

Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Subjects will receive placebo for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Period Title: Overall Study
Started 9 9
Sodium Restriction Baseline Visit [1] 9 9
Sodium Loading Baseline Visit [2] 9 9
Post-randomization Sodium Restriction [3] 9 9
Post-Randomization Sodium Loaded [4] 9 9
Completed 9 9
Not Completed 0 0
[1]
The first study visit was a pre-randomization assessment while sodium restricted (Baseline)
[2]
The second study visit was a pre-randomization assessment while sodium loaded (Baseline)
[3]
This visit was an assessment while sodium restricted and following 3 weeks of study medication
[4]
This visit was an assessment while sodium loaded and following 3 weeks of study medication
Arm/Group Title Calcitriol Placebo Total
Hide Arm/Group Description

Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Subjects will receive placebo for 3 weeks.

Subjects have their renin-angiotensin system, renal plasma flow, and urine protein assessed at baseline while sodium restricted and sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat assessments again while sodium restricted and sodium loaded.

Total of all reporting groups
Overall Number of Baseline Participants 9 9 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
  88.9%
9
 100.0%
17
  94.4%
>=65 years
1
  11.1%
0
   0.0%
1
   5.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 9 participants 18 participants
51.0  (10.4) 50.7  (5.0) 50.8  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
Female
2
  22.2%
5
  55.6%
7
  38.9%
Male
7
  77.8%
4
  44.4%
11
  61.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 9 participants 9 participants 18 participants
9
 100.0%
9
 100.0%
18
 100.0%
1.Primary Outcome
Title The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy
Hide Description The below results represent the change in Plasma Renin Activity.
Time Frame baseline and 2 weeks following calcitriol/placebo therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Calcitriol Placebo
Hide Arm/Group Description:
Subjects have their plasma renin activity assessed at baseline while sodium restricted, and again after 2 weeks of randomized therapy with calcitriol (up to 0.75 mcg daily) or placebo.
Subjects have their plasma renin activity assessed at baseline while sodium restricted, and again after 2 weeks of randomized therapy with calcitriol (up to 0.75 mcg daily) or placebo.
Overall Number of Participants Analyzed 9 9
Median (Inter-Quartile Range)
Unit of Measure: ng/mL/h
0
(-1.3 to 0.3)
-1.3
(-3.6 to -0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcitriol, Placebo
Comments The hypothesis was that calcitriol therapy would lower plasma renin activity (PRA), when sodium restricted, when compared to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 1.3
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Renal Plasma Flow After Calcitriol/Placebo Therapy
Hide Description Subjects had their renal plasma flow assessed at baseline while sodium loaded, and again after 3 weeks of randomized therapy with either calcitriol (up to 0.75 mcg daily) or placebo.
Time Frame baseline and 3 weeks following calcitriol/placebo therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Calcitriol Placebo
Hide Arm/Group Description:
Subjects have their renal plasma flow assessed at baseline while sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat renal plasma flow assessments again while sodium loaded.
Subjects have their renal plasma flow assessed at baseline while sodium loaded. They will then be randomized to receive calcitriol (up to 0.75 mcg daily) or placebo for 3 weeks, and repeat renal plasma flow assessments again while sodium loaded.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m2
-16.4  (180.5) -0.6  (142.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcitriol, Placebo
Comments The hypothesis was that calcitriol therapy would raise renal plasma flow, when sodium loaded, when compared to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.8
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Urine Protein After Calcitriol/Placebo Therapy
Hide Description Subjects have their urine protein assessed at baseline while sodium loaded and again 3 weeks after randomized therapy with calcitriol or placebo.
Time Frame baseline and 3 weeks following calcitriol/placebo therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Calcitriol Placebo
Hide Arm/Group Description:
Subjects have their urine protein assessed at baseline while sodium sodium loaded and again following 3 weeks of randomization to calcitriol (up to 0.75 mcg daily) or placebo.
Subjects have their urine protein assessed at baseline while sodium sodium loaded and again following 3 weeks of randomization to calcitriol (up to 0.75 mcg daily) or placebo.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: mg/24h
21.1  (95.7) 8.1  (51.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Calcitriol, Placebo
Comments The hypothesis was that calcitriol therapy would lower urine protein, when sodium loaded, when compared to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.0
Estimation Comments [Not Specified]
Time Frame They were collected for the duration of the study (~4 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Calcitriol Placebo
Hide Arm/Group Description

Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.

Calcitriol: Subjects will receive calcitriol (up to 0.75 mcg daily) for 3 weeks.

Subjects will receive placebo for 3 weeks.

Placebo: Subjects will receive placebo for 3 weeks.

All-Cause Mortality
Calcitriol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Calcitriol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/9 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Calcitriol Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/9 (0.00%) 
This was a small physiological study, not a treatment study or a typical Phase 1-4 study. The objective was to investigate the mechanistic link between vitamin D receptor agonist therapy and the renin-angiotensin system.
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
Name/Title: Dr. Anand Vaidya (Asst Professor of Medicine)
Organization: Brigham and Women's Hospital
Phone: 6175258285 ext 617
Responsible Party: Anand Vaidya, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01635062     History of Changes
Other Study ID Numbers: 2012P000905
First Submitted: July 2, 2012
First Posted: July 6, 2012
Results First Submitted: January 6, 2017
Results First Posted: April 11, 2017
Last Update Posted: April 11, 2017