EAL

MNT: Comparative Effectiveness of MNT Services (2009)

Citation:

Dolecek TA, Bradham KH, Espeland MA, Margitic SE, Byington RP, Hoen H, Kappelle LJ, for the Asymptomatic Carotid Artery Progression Study (ACAPS) Group. Maximizing recruitment efforts in a drug lipid-lowering trial with dietary intervention to lower LDL cholesterol. Controlled Clinical Trials. 1996; 17(1): 33-45.

PubMed ID: 8721800

Study Design:

Non-Randomized Controlled Trial

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To describe the pre-randomization intensive dietary intervention used in ACAPS and present findings resulting from its implementation.

Inclusion Criteria:

Screening visit 1: Cholesterol eligible (180 to 300mg per dL)
Screening visit 2 (Slow Track): LDL 160 to 189mg per dL with more than two risk factors; LDL 190 to 210mg per dL with less than one risk factor
Screening visit 2 (Fast Track): LDL 130 to 159mg per dL with any risk factors; LDL 160 to 189mg per dL with less than one risk factor
Screening visit 3: Ultrasound eligible, run-in medications dispensed.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

A select group of screened applicants initially disqualified from a four-center, primary prevention drug lipid-lowering trial because of borderline elevated serum low-density lipoprotein cholesterol levels participated in a dietary intervention protocol that was incorporated into the screening phase of the trial. 77 screened applicants for the Asymptomatic Carotid Artery Progression Study (ACAPS) entered the dietary program. ACAPS was a multi-center, double-blind, placebo-controlled trial of asymptomatic individuals with early carotid atherosclerosis; the trial was designed to test the effects of the serum cholesterol-lowering drug lovastatin on progression of early atherosclerotic lesions in the carotid arteries.

Design

Non-randomized clinical trial, pre-randomization screening protocol for randomized controlled trial.

Intervention

ACAPS screening process involved three pre-randomization visits spaced approximately one month apart
Dietary program was overseen by an experienced Registered Dietitian at the central operations site who collaborated with local staff at clinical sites during program implementation
National Cholesterol Education Program-Adult Treatment Panel I (NCEP-ATP I) fat-modified step I diet specifications served as the basis for the intervention
The program consisted of five sessions conducted over an eight-week period and primarily used written and audiovisual educational materials in combination with behavioral approaches
First session was an individual session conducted by on-site dietitians followed by four group sessions that were led by either a locally trained registered dietitian or a clinic staff member.

Statistical Analysis

Paired T-tests and repeated measures of covariance were used to examine differences in participants' blood lipids, body weight and reported nutrient intake over time
Differences in sociodemographics and in pre-intervention measures of serum lipid levels, BMI and daily nutrient intake estimates between participants that were responders, non-responders and dropouts to the dietary intervention were assessed with chi-square or Fisher's exact tests for categorical variables and analysis of variance or analysis of covariance for continuous variables
Pearson correlations were used to describe relationships between blood lipid changes from the intervention and pre-intervention values.

Data Collection Summary:

Timing of Measurements

ACAPS screening process involved three pre-randomization visits spaced approximately one month apart.

Dependent Variables

Serum total cholesterol determination assessed by reflotron analyzer
Abbreviated B-mode ultrasound of the carotid arteries to identify possible quantifying lesions as reflected by defined intimal-medial wall thickening measurements
Fasting blood samples for lipid profiles and assessment of liver function
Risk factor status as defined by NCEP-ATP I guidelines
Dietary data collected through self-administered food frequency questionnaire.

Independent Variables

Dietary program was overseen by an experienced Registered Dietitian at the central operations site who collaborated with local staff at clinical sites during program implementation
National Cholesterol Education Program-Adult Treatment Panel I (NCEP-ATP I) fat-modified step I diet specifications served as the basis for the intervention
The program consisted of five sessions conducted over an eight-week period and primarily used written and audiovisual educational materials in combination with behavioral approaches
First session was an individual session conducted by on-site dietitians followed by four group sessions which were led by either a locally trained Registered Dietitian or a clinic staff member.

Description of Actual Data Sample:

Initial N: 77 screened applicants entered the dietary program
Attrition (final N): 65 subjects (36 responders, 29 non-responders); 12 dropped out (16%)
Anthropometrics: Analyses comparing pre-intervention characteristics of responders, non-responders and dropouts showed no differences among groups in age, CHD risk factors, BMI, baseline serum lipid levels or relevant nutrient intake estimates with the exception that dropouts tended to be smokers and had lower LDL-C levels
Location: Several centers in the United States.

Summary of Results:

Variables	Change from Screening Visit 2A-2	P-Value	Change from Screening Visit 3-2A	P-Value
Total cholesterol (mg per dL)	-31.7	<0.001	+1.7	0.24
LDL cholesterol (mg per dL)	-28.9	<0.001	+0.6	0.59
HDL cholesterol (mg per dL)	-4.8	<0.001	+1.0	0.39
Triglycerides (mg per dL)	+10.2	0.29	+1.5	0.63
Body weight (pounds)	-7.2	<0.001	NA	NA

Other Findings

36 responded to the intervention by achieving their LDL-cholesterol goal; responders achieved an average 11.7% drop in total cholesterol (32mg per dL or 0.83mmol per L) at the end of the eight-week program and were randomized into ACAPS.

Mean LDL-cholesterol decline of 15.1% paralleled total cholesterol change.

HDL-cholesterol also decreased significantly (9.6%).

A significant mean weight loss of over five pounds was observed for responders after eight weeks.

These results were sustained for 24 of the responders attending the final screening visit approximately one month later, when another fasting blood lipid measurement was made.

Pre- and post-intervention nutrition data assessed by semiquantitative food frequency questionnaire for 20 screenees randomized into the study indicated significant reductions in total fat, saturated fat, polyunsaturated fat and dietary cholesterol, all known to influence blood lipid levels.

Author Conclusion:

We demonstrated that a relatively uncomplicated dietary intervention could be effective as a recruitment strategy in a primary prevention drug lipid-lowering trial by reducing LDL-cholesterol levels to meet NCEP-ATP I guidelines. Our approach produced a yield of 22 participants, 29% of the total subgroup, who would have been lost during the screening process because of borderline high LDL-cholesterol levels. Similar programs may prove useful to other drug lipid-lowering trials to maximize recruitment efforts.

Funding Source:

Government:

NIH/NHLBI Grant R01HL38194

Industry:

Reviewer Comments:

Subjects were not well described in terms of age, ethnicity, etc. Physical activity was not addressed. Authors note that involvement of ACAPS staff other than nutritionists in delivering the dietary intervention program group sessions and collecting the dietary data made this study component an integral part of the trial by promoting the team approach.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		???
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	N/A
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		???
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes