Polyp Prevention Trial
Condition: Diet; Polyps; Adenoma
MeSH terms: Adenoma; Polyps
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary objective of the Poly Prevention Trial (PPT) is to determine whether a low fat,
      high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous
      polyps of the large bowel. Secondary objectives of the PPT include 1) evaluating the
      effectiveness of the intervention program with respect to participant achievement of dietary
      goals; 2) examining the relation of dietary change and biochemical markers in blood; and 3)
      assessing the impact of the intervention on quality of life indicators.
    

Detailed description: 
      OBJECTIVES:

      The primary objective of the Polyp Prevention Trial (PPT) is to determine whether a low fat,
      high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous
      polyps of the large bowel. Secondary objectives of the PPT include 1) evaluating the
      effectiveness of the intervention program with respect to participant achievement of dietary
      goals; 2) examining the relation of dietary change and biochemical markers in blood; and 3)
      assessing the impact of the intervention on quality of life indicators.

      BACKGROUND:

      Nearly 60,000 men and women will die from large bowel cancer in the United States this year,
      making it the second leading cause of death from malignant disease in this country. The
      evidence that diet plays a key role in large bowel carcinogenesis is strong and growing. The
      PPT was undertaken because it is unlikely, with respect to diet and large bowel cancer, that
      any combination of further animal research, clinical investigations employing non-neoplastic
      endpoints, or observational epidemiologic studies would be sufficiently persuasive to
      influence public health policy.

      A large body of ecologic, analytic epidemiologic, human metabolic, and animal experimental
      data suggests that three dietary factors increase the risk of large bowel cancer: high
      dietary fat, low dietary fiber, and low vegetable and fruit intake. Previous dietary
      intervention studies have generally focused on a single nutrient. The PPT is unique in that
      three dietary factors are being investigated simultaneously through intervention with a
      realistic, comprehensive dietary pattern change. NCI investigators adopted this multiple-goal
      dietary intervention strategy in the PPT for several reasons: people eat foods, not isolated
      nutrients; there may be unknown protective food constituents not encompassed in a
      single-nutrient intervention; and there may well be important synergistic effects of various
      food components best captured in a comprehensive, multifactor dietary pattern. Moreover, by
      embracing three promising dietary hypotheses simultaneously, the PPT intervention is intended
      to maximize the possibility of reducing polyp recurrence. The direct demonstration of any
      effect of diet on the large bowel neoplastic process would be a major advance.

      Large bowel adenomas (polyps) present a unique opportunity to conduct an intervention trial
      because of the high prevalence of these lesions in the general population (over 30% in adults
      over 50 years of age), the high polyp recurrence rate (at least 10% annually) in those who
      have undergone adenoma removal, and the strong link between adenomas and cancer (the
      so-called adenoma-carcinoma sequence). It is generally accepted that large bowel adenomas are
      an obligate precursor lesion for most large bowel cancers. An intervention reducing the
      recurrence of large bowel polyps would thus have a strong likelihood of reducing the
      incidence of large bowel cancer.

      DESIGN:

      The PPT is a randomized, controlled trial being carried out at eight Clinical Centers in the
      United States. The Data and Nutrition Coordinating Center (DNCC) is Westat, Inc., Rockville,
      Maryland. The target sample size of 2000 permits the detection with 90% power of a reduction
      of 24% in the polyp recurrence rate.

      The dietary goals for the intervention arm are 20% of calories from fat, 18g fiber/1000 kcal,
      and 5-8 servings of fruits and vegetables (the exact number based on caloric intake). The
      usual (control) diet, based on data from national surveys, is expected to comprise
      approximately 35% of calories from fat, 10-15 g per day of dietary fiber, and 3.5 servings of
      vegetables and fruits daily.

      The overall strategy for the intervention program is to reduce calories from fat and to
      replace them with calories from fruits vegetables and grains thus increasing dietary fiber
      intake. The intervention program, patterned after the approach used in the feasibility phase
      of the Women's Health Trial, integrates nutrition education and behavior modification
      techniques. Although initial counseling sessions are carried out one-on-one by the PPT
      nutritionists, most intervention group members participate in group counseling after the
      first year.

      The control group is not offered a nutrition intervention program since the general strategy
      adopted for this group will be minimum interference with customary diets while collecting
      nutritional data considered necessary for appropriate comparison with the nutrition
      intervention group. Subjects in the control group are expected to maintain their usual diet.

      Three different dietary assessment instruments are used in the PPT: a modified Block/NCI Food
      Frequency Questionnaire (FFQ), Four Day Food Records (4DFR), and 24 Hour Recalls.

      Participants undergo colonoscopy again at one (T1) and four (T4) years into the study. Over
      280 endoscopists participating in the PPT carry out the T1 and T4 colonoscopies. Although the
      recurrence of one or more adenomas is the primary endpoint of the study, it will also be
      possible to relate the dietary intervention to number, size, and histotype of polyps. Because
      some polyps (10-15%) tend to be missed at baseline, the primary analytic interval (on which
      sample size calculations were based) is T1 through T4.

      The presence of one or more adenomas at the qualifying colonoscopy--a key eligibility factor
      for PPT--was determined by Clinical Center trial pathologists who had been previously
      oriented by the central pathologists to PPT pathologic criteria. The number, size, and
      location of adenomas at baseline was determined by the participating endoscopists. To
      standardize the histologic diagnoses used in endpoint ascertainment, the PPT requires that
      histologic type and extent of atypia be determined by the central pathologists for all
      lesions removed at baseline, T1, and T4.

      Blood specimens are collected on all participants annually; these are analyzed on a 20%
      participant sample (the same individuals for whom the diet records are analyzed) for lipids,
      carotenoids, and vitamins A and E. Blood specimens are also available for other analyses
      including hormone and molecular genetic analysis.
    

Intervention name(s): low fat, high fiber, high fruit and vegetable eating plan
Intervention type(s): Other
Intervention description(s): Participants were randomized to a low fat, high fiber, high fruit and vegetable (intervention arm) or their usual diet (control arm)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Intervention; Diet; Colon