Calcium and Vitamin D Trial
Overview
Previous research on dietary or supplemental calcium suggested that increased intake is associated with a decreased risk of osteoporosis and with increased bone density. Vitamin D is often added to calcium to increase absorption in the body. The effects of calcium and vitamin D on fracture incidence, had not been determined. The WHI Calcium and Vitamin D Trial (CaD) was designed to test the effects of calcium and vitamin D supplementation on women’s risk for hip fractures (primary analyses), and other fractures and colorectal cancer (secondary analyses). Previous research on calcium and vitamin D and disease outcomes, as background to the CaD trial, are reviewed in the WHI Protocol.
Participants randomized to the WHI Clinical Trial (HT or DM) were eligible for the CaD Trial 12-24 months after randomization. Eligibility criteria for the CaD were focused on safety and competing risks (e.g., no medical condition associated with survival of less than three years). Participants were eligible for the CaD even if taking their own supplemental calcium or vitamin D, although their personal use of vitamin D had to be 600 IU or less, for safety reasons. A total of 36,282 CT participants were also randomized in the CaD. Baseline characteristics of these participants are outlined in the CaD baseline monograph.
Intervention
Participants in CaD were randomized in a 1:1 fashion to one of two arms:
Calcium carbonate with 1000 mg of elemental calcium combined with vitamin D3 400 IU per day, taken in two divided doses daily
Placebo, taken as one pill twice a day
CaD study pills were initially available in a chewable (peppermint-flavored) format only. Because some participants did not tolerate this formulation well (e.g., didn’t like the taste or texture), an optional swallow-able formulation was developed and offered, starting in July 1997, to eligible participants (who were offered a visual inspection and/or “taste test”) before randomization and to all randomized CaD participants during follow-up visits. Participants were told that they could switch between the chewable and swallow-able formulations at any contact during which new study pills were dispensed. At randomization all CaD participants were given a “CaD Information Sheet” (which was revised to a more detailed “CaD Handbook” in late 2002). This participant material was offered each time study pills were dispensed and included trial-specific information about:
Safety (e.g., notifying staff if high blood calcium or bladder or kidney stones are diagnosed)
Adherence (e.g., taking study pills daily, managing symptoms)
Retention (e.g., coming in for clinic visits)
Follow-up
Data Collection
CaD participants were contacted by phone 4 weeks after randomization to complete a management (e.g., symptoms, adherence, and pill tolerance) and safety interview, which was repeated semi-annually thereafter while the participant was taking study pills. CaD participants, otherwise, had routine contacts based on their CT follow-up schedule. Follow-up data collected in CT and, specifically, CaD participants can be found under Frequency of Data Collection.
If symptom or safety concerns or adherence challenges were noted, these concerns were evaluated and addressed during participant contacts by trained staff and followed-up appropriately.
Symptom Management
Participants were advised on self-care strategies for managing symptoms, such as constipation or bloating. In addition, Clinical Center staff were provided with specific guidelines for temporary “step-down” of study pills (e.g., to one pill a day) in the event that participants were experiencing symptoms or difficulties with taking their study pills. There were no protocol-mandated reasons for unblinding CaD participants’ treatment arm. In the unusual event that unblinding was carried out, no clinic staff other than the principal investigator or consulting physician were unblinded to treatment arm.
Protocol-Mandated Reasons for Discontinuing Study Pills
CaD study pills were discontinued, without unblinding treatment arm, for participants who developed certain health conditions or began taking certain prescription medications. Problems that may have affected continuation of study pills are described in the CaD section of the staff procedures manual (below).
Related publications
Baseline monograph
Main trial findings
See Also