SANDS: Stop Atherosclerosis in Native Diabetics Study

• Sponsor: Cynthia West (Other)
• Overall Status: Completed
• CT.gov ID: NCT00147251
• Collaborator: (none)
• Enrollment: 548
• Locations: 4
• Arms: 2
• Duration (Months): 48
• Patients Per Site: 137
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

Compared to standard treatment goals achieving lower targets for LDL cholesterol (bad cholesterol) and blood pressure in people with diabetes will slow the progression of atherosclerosis as measured by carotid artery thickness, and reduce clinical cardiovascular events such as heart attacks and strokes. This study is a randomized 3-year trial. The primary endpoint will be a combination of various measures of the carotid artery, (which is an easy, non-invasive way to detect cardiovascular disease) and events such as heart attacks and strokes. The study will also look at secondary endpoints such as how well the heart pumps, fat,protein and inflammatory markers in the blood,and kidney function. The study enrolled 549 American Indian men and women with diabetes, > 40 years of age and is being conducted in four field centers involving Indian Health Service/Tribal primary care facilities in Phoenix/Sacaton, Arizona; Chinle, Arizona; Rapid City/Pine Ridge, South Dakota; and Lawton, Oklahoma, with input from American Indian physicians and community members.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease; Hypertension; Hyperlipidemia; Diabetes; Carotid Atherosclerosis	Drug: FDA approved drugs to treat blood pressure and cholesterol	Phase 4

Detailed Description

Diabetes incidence is increasing rapidly in the United States. Diabetes increases the risk for CVD, the major cause of death in diabetic individuals. The conventional cardiovascular risk factors of hyperlipidemia and hypertension add to the progression of diabetic vascular disease. Appropriate treatment targets for LDL-C and blood pressure in diabetic individuals are currently being debated. The Stop Atherosclerosis in Native Diabetics Study is a randomized, open label, 3-year, clinical trial to examine the effects of aggressive LDL-C (goal < 70 mg/dL) and BP (goal < 115/75 mm Hg) reduction versus the standard goals of < 100 mg/dL for LDL-C and < 130/85 mmHg for BP. Five hundred forty-nine American Indian men and women > age 40 with type 2 diabetes were randomized to one of two groups. Lipids and BP are managed using FDA-approved medications in an algorithmic approach. The presence and progression of atherosclerosis are evaluated by carotid ultrasonography; echocardiography assesses cardiac function. The primary endpoint is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events. These outcomes are combined by using a ranked analysis for carotid thickness and assigning a "worst rank" for a cardiovascular event. Secondary endpoints include carotid plaque score, left ventricular geometry and function, serum CRP, and safety measures. Unique aspects of the study design and analysis plan involve changes during the trial of LDL-C treatment goals for participants with baseline or incident CVD in the conventional group, because of changes in the standard of care, and the use of a composite outcome. Study results will be valuable in understanding the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in all U.S. populations and will provide evidence for determining optimal LDL-C and BP treatment goals for diabetic patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 548 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Stop Atherosclerosis in Native Diabetics Study
• Study Start Date: May 1, 2003
• Actual Primary Completion Date: Nov 1, 2006
• Actual Study Completion Date: May 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: SANDS Control Group Standard Treatment for blood pressure and cholesterol
Active Comparator: SANDS Intervention Group FDA approved drugs to treat blood pressure and cholesterol	Drug: FDA approved drugs to treat blood pressure and cholesterol; Other Names: No Intervention

Outcome Measures

Primary Outcome Measures

1. Changing LDL Cholesterol [36 months]

   LDL cholesterol intervention to lower targets than are currently recommended to retard atherosclerosis measured by LDL-C mg/dL. Scale: LDL cholesterol levels should be less than 100 mg/dL

Secondary Outcome Measures

1. Changing Blood Pressure [36 month follow-up]

   Treatment of blood pressure to prevent/reduce diseases of heart and blood vessels. Measured by mmHG. Normal values should be below 120/80 mm Hg.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. American Indian men and women 40 years of age or older

2. Type 2 DM (according to 1997 ADA criteria and/or previously diagnosed by former ADA or WHO criteria): fasting plasma glucose >= 7.0 mmol/L (126 mg/dL) or 2-hour glucose >= 11.0 mmol/L (>200 mg/dL) after a 75-gram oral glucose tolerance test.

3. LDL cholesterol >= 100 mg/dL. within the previous 12 months.

4. Systolic BP >= 130 mm Hg. within the previous 12 months.

Exclusion Criteria:

1. New York Heart Association Stage III- IV congestive heart failure.

2. SBP >180 mmHg (2% of population) or patients with known causes of hypertension.

3. History of angioedema.

4. Any medical condition that study physicians believe would interfere with study participation or evaluation of results.

5. Mental incapacity and/or cognitive impairment on the part of the patient that would preclude adequate understanding of, or cooperation with, the study protocol.

6. Serum hepatic transaminase levels 2X the upper limit of normal.

7. Participation in any clinical trial of any investigational medication within 3 months prior to this trial.

8. Renal insufficiency as indicated by serum creatinine >2.0 for women and >2.4 for men.

9. Diagnosis of primary hyperlipidemia in medical record.

10. Secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome. Patients on stable doses of thyroid replacement therapy will be eligible.

11. Presence of malignancy or history of any cancer except skin cancer within the past 5 years.

12. Pregnancy or lactation. Premenopausal women will be requested to use birth control methods throughout the study and provided educational materials about the risks of using the study medications during pregnancy.

13. Unable to obtain quantifiable carotid measure during screening examination.

14. Concomitant long term use of cyclosporins (Sandimmune), macrolide antibiotics (erythromycin -many generic and brand name forms, clarithromycin, Biaxin, and Zithromax), azole antifungals (itraconazole-Sporanox, ritonavir, Norvir, and nelfinavir (Viracept).

15. Orthostatic hypotension as defined by the following:

16. The individual has a measured fall of >20 mmHg in systolic BP upon standing associated with symptoms lasting more than one minute (or severe symptoms that would not allow further lowering of BP)

17. The standing systolic blood pressure is less than 90 mm.

18. Triglyceride level >350 mg/dl.

19. Severe aortic stenosis with valve area <=1.0 square cm.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chinle Comprehensive Health Care	Chinle	Arizona	United States	86503
2	Phoenix Indian Medical Center	Phoenix	Arizona	United States	85016
3	USPHS Indian Hospital	Lawton	Oklahoma	United States	73507
4	Black Hills Center for American Indian Health	Rapid City	South Dakota	United States	57701

Sponsors and Collaborators

• Cynthia West

Investigators

• Principal Investigator: Barbara V Howard, PhD, Medstar Health Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cynthia West, Phoenix Field Office Manager, Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT00147251
• Other Study ID Numbers: 2000-285; Grant # 1 U01 HL67031; NCT00047424
• First Posted: Sep 7, 2005
• Last Update Posted: Jul 7, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Cynthia West, Phoenix Field Office Manager, Medstar Health Research Institute: lowering LDL and BP below current targets; LDL cholesterol treatment; blood pressure treatment; carotid intimal medial thickness; prevent progression of CVD
• Additional relevant MeSH terms: Carotid Artery Diseases; Cardiovascular Diseases; Atherosclerosis; Hyperlipidemias

Study Results

Participant Flow

Recruitment Details	Participants were identified from the local Indian hospital service center, or DM clinic. In March 2004, the DSMB recommended and the SC voted to over-recruit by 10-20% to compensate for the possible need for more aggressive treatment for participants with baseline CVD. Randomization concluded in July 2004 with 547 randomized participants.
Pre-assignment Detail	Sonogram eligibility was confirmed by tape review at the core lab prior to randomization. A potential participant had to have LDL-C > 100 mg/dL and systolic BP > 130/85 mmHg. A participant could undergo a maximum of four screening visits within a 3-month period to confirm eligibility.

Arm/Group Title	Standard Treatment	Aggressive Treatment
Arm/Group Description	standard targets of LDL-C < 100 mg/dL and BP < 130/85 mm Hg	/aggressive targets of LDL-C < 70 mg/dL plus BP < 115/75 mm Hg
Period Title: Recruitment and Enrollment
STARTED	271	277
COMPLETED	247	252
NOT COMPLETED	24	25
Period Title: Recruitment and Enrollment
STARTED	247	252
COMPLETED	247	252
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard Treatment	Aggressive Treatment	Total
Arm/Group Description	standard targets of LDL-C < 100 mg/dL and BP < 130/85 mm Hg	/aggressive targets of LDL-C < 70 mg/dL plus BP < 115/75 mm Hg	Total of all reporting groups
Overall Participants	247	252	499
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.9 (4.24)	55.3 (4.24)	56.1 (4.24)
Sex: Female, Male (Count of Participants)
Female	163 66%	164 65.1%	327 65.5%
Male	84 34%	88 34.9%	172 34.5%

Outcome Measures

1. Primary Outcome

Title	Changing LDL Cholesterol
Description	LDL cholesterol intervention to lower targets than are currently recommended to retard atherosclerosis measured by LDL-C mg/dL. Scale: LDL cholesterol levels should be less than 100 mg/dL
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Native American

Arm/Group Title	Standard Treatment	Aggressive Treatment
Arm/Group Description	standard targets of LDL-C < 100 mg/dL and	/aggressive targets of LDL-C < 70 mg/dL
Measure Participants	247	252
Median (Standard Deviation) [Mg/dl]	100 (74)	70 (91)

2. Secondary Outcome

Title	Changing Blood Pressure
Description	Treatment of blood pressure to prevent/reduce diseases of heart and blood vessels. Measured by mmHG. Normal values should be below 120/80 mm Hg.
Time Frame	36 month follow-up

Outcome Measure Data

Analysis Population Description

American Indian

Arm/Group Title	SANDS Control Group	SANDS Intervention Group
Arm/Group Description	Standard Treatment for blood pressure	FDA approved drugs to treat blood pressure
Measure Participants	247	252
Mean (Standard Deviation) [mm Hg]	130 (.001)	115 (.001)

Adverse Events

Time Frame	3 years
Arm/Group Title	SANDS Control Group		SANDS Intervention Group
Arm/Group Description	Standard Treatment for blood pressure and cholesterol		FDA approved drugs to treat blood pressure and cholesterol
All Cause Mortality
	SANDS Control Group		SANDS Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SANDS Control Group		SANDS Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/247 (0.4%)		4/252 (1.6%)
Vascular disorders
Heart Attack	1/247 (0.4%)	1	4/252 (1.6%)	4
Other (Not Including Serious) Adverse Events
	SANDS Control Group		SANDS Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/247 (0%)		0/252 (0%)

Limitations/Caveats

[Not Specified]

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.