This proposal seeks to extend the Dietary Intervention Study in Children (DISC I), a randomized clinical trial of dietary intervention in children with elevated LDL-cholesterol (LDL-C). The primary aims of the extension are to ascertain adult height attained and to determine the long-term effect of the intervention on LDL-C and total cholesterol. Coronary heart disease (CHD) remains the leading cause of premature death and disability in the U.S. and there is convincing evidence of the development of atherosclerosis during childhood, but the long-term safety and efficacy of a cholesterol-lowering diet in children and adolescents have not been established. Six clinical centers and a Coordinating Center were funded for the period December 4, 1986, to January 31, 1994, to carry out a clinical trial designed to assess the impact of such dietary intervention in children age 8-10 with elevated LDL-C levels. The clinical centers identified and enrolled 663 children (mean LDL-C 131 mg/dl), randomly assigned to an intervention (IG) or a usual care group (CG). Dietary goals of intervention are <28% of total calories from fat, <8% from saturated fatty acids, 9% from polyunsaturated fatty acids, and <75 mg. of dietary cholesterol per 1000 kcal. For DISC I, the primary efficacy outcome is the 36-month change in LDL-C, and the primary safety outcomes are attained height and serum ferritin at 36 months. Results to date indicate a significantly greater reduction of LDL-C in the IG than in the CG at 12 and 36 months, with no significant adverse effects on growth in the IG. An extension of DISC is necessary to provide an unequivocal answer to the safety question without the confounding influence of maturation on growth, allowing the ascertainment of final adult stature. The present submission requests funding for a 7-year extension of the study, from February 1, 1994, to January 31, 2001 (DISC II), to follow the participants until they reach age 18. Intervention will consist of at least two face-to-face contacts with each IG participant per year and other contacts at more frequent intervals. Follow-up will consist of annual assessments of height, weight, and maturation, with dietary assessment and lipid measurements at years 5 and 7 and at the final visit nearest the 18th birthday. It is anticipated that at least 85% of DISC I participants will be successfully followed. This population offers the unique possibility not only to fulfill successfully the primary aims of DISC II, but also to make a number of other important observations in these children as they grow through adolescence into early adulthood.
