Doubly Labeled Water Central Laboratory for Clinical Trials of Caloric Restriction

Notice Number: NOT-AG-04-007

Key Dates
Release Date: September 3, 2004
Response Due Date: November 10, 2004

Issued by
National Institute on Aging (NIA), (http://www.nia.nih.gov/)

Purpose

The National Institute on Aging (NIA) is conducting a set of human intervention studies collectively titled “Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE).” Measurement of total energy expenditure (TEE) is an important component of CALERIE, and is being performed using the doubly-labeled water (DLW) technique. This method is considered to provide the most accurate assessment of free-living, daily energy expenditure. The NIA is interested in obtaining information from the academic and industrial community as to the capabilities, precision of testing, and quality control procedures of laboratories equipped with the mass spectrometers that are able to perform DLW assays and that could serve as a central laboratory for DLW assays of TEE in CALERIE. Specifically, the NIA is interested in identifying laboratories that are capable of preparing and/or analyzing substantial numbers of samples on an ongoing basis with short turnaround time, experienced in working with outside clinics, and able to provide high quality DLW results.

Background

Numerous studies in laboratory animals have shown that chronic caloric restriction (CR) extends maximum and average life span by as much as 40% and delays many age-related pathologies correspondingly. The implications of these findings regarding the effects of voluntary CR on life span and development of age-related diseases in humans are unknown.

In 1999, NIA, with collaboration and advice from NIDDK, convened the Caloric Restriction Clinical Implications Advisory Group. The Advisory Group recommended that controlled human intervention studies of caloric restriction in non-obese persons over a period of at least two years be initiated to determine effects of CR interventions on physiology, body composition, and risk factors for age-related pathologies.

Because accurate determination of participants’ caloric intake is an essential component of such studies, the NIA Advisory Group recommended that caloric intake in CR intervention studies be determined using DLW- based methodologies.

The DLW method is based upon the principle that oxygen atoms in body water and exhaled CO2 are in equilibrium. Oxygen atoms are eliminated from the body as both H2O and exhaled CO2 whereas hydrogen atoms are eliminated as H2O only. Therefore, the difference between the elimination rates of oxygen and hydrogen from body water represents a measure of CO2 flux from where TEE can be calculated.

The calculated TEE, along with changes in body energy stores during the DLW period is used to determine the energy intake for each CALERIE participant before and at several time points over the intervention period.

NIA is supporting CALERIE, which consists of three phases:

Phase 1 or Pilot Phase: Protocol refinement and pilot studies (up to 2 years). Approximately 140 subjects have being studied in Phase 1, which is expected to end in 2005.

Phase 2: Protocol Implementation (interventions testing and preliminary analysis of data). The determination of the number of subjects for Phase 2 will depend in part on the results in Phase 1, but approximately 350 participants maybe studied.

Phase 3: Data analysis and reporting (approximately 1 year).

The use of DLW determination of TEE is a crucial element in CALERIE for:

CALERIE Phase 1 is approaching its completion, and important decisions and arrangements for Phase 2 are to be made in the near future. One of these arrangements includes identifying an appropriate laboratory that is capable of performing as many as several thousand TEE determinations using the DLW method within a three-year period to meet the requirements for Phase 2 studies.

Information Requested

The NIA seeks your help in identifying a potential laboratory that is: a) able to negotiate the purchase of large amounts (up to 360 kg) of 10% of H218O and 2H2O or the equivalent in higher concentration; b) capable of preparing and analyzing several thousand samples within a three-year period for H218O and 2H2O abundances by isotope ratio mass spectrometry; or c) capable of analyzing the above-indicated number of samples that are prepared by another laboratory. A laboratory must have experience in mass spectrometry; experience in the DLW method is desired but not required.

Your thoughts, ideas, and suggestions will help the NIA refine its strategy and requirements, and identify a laboratory meeting the CALERIE study DLW assay needs. Respondents are asked to provide information about laboratories in regard to the following aspects. However, the information presented need not be limited to these areas.

1. Specify number, technical characteristics and configurations of the mass spectrometers that are able to analyze samples for H218O and 2H2O abundances by isotope ratio mass spectrometry. Describe the DLW assay and TEE calculation methods employed at the laboratory if laboratory performs DLW assays.

2. Provide the current (if any) and potential laboratory’s DLW analytical capacity and indicate the maximum number of TEE determinations per week that laboratory is able to perform.

3. Specify analytical and within subject coefficient of variation for TEE determination (if any) and indicate quality control measures aimed at decreasing the coefficients of variation.

4. Indicate down time (in days) over the past two years due to equipment failures, waiting for parts, or other technical problems.

5. Describe data management and data transmission procedures employed at the laboratory.

6. Indicate the specimen turnaround time from a sample received at the laboratory to results sent to a clinic.

7. Specify sample storage capacity at the laboratory.

8. Describe standard laboratory operating procedures, staff training requirements, and quality assurance/quality control program for the laboratory.

9. Describe experience (if any) in: a) acquiring of 10% H218O DLW, including approximate quantities that can be acquired, and b) arranging shipments of DLW to the clinical sites.

10. Specify the cost of assay per participant, including and excluding the cost of DLW.

11. Describe experience in receiving samples from, transmitting data to and interacting with multiple study sites and/or coordinating center located geographically separate.

Response and Process

This Request for Information (RFI) is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the NIA. The purpose of this RFI is to identify potential laboratories that may be interested in and capable of meeting the requirements for DLW analysis in Phase 2 of the CALERIE study. The NIA does not intend to award a contract on the basis of responses to this RFI nor otherwise pay for the preparation of any information submitted or NIA’s use of such information. Acknowledgment of receipt of responses will not be made, nor will respondents be notified of the NIA’s evaluation of the information received. No basis for claims against the NIA shall arise as a result of a response to this RFI or the NIA’s use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement.

Response in any of the areas is welcome; respondents should not feel compelled to address all items. Please respond no later than November 10, 2004. We look forward to your thoughts, opinions, and suggestions, and hope you will share this document with your colleagues. All responses will be kept confidential.

To respond, please send a letter, fax, or email to the following address:

Sergei V. Romashkan, MD, PhD
Clinical Trials Branch
Geriatrics and Clinical Gerontology Program
National Institute on Aging
Gateway Building, Suite 525A
7201 Wisconsin Avenue
Bethesda, MD 20892-9205
(Fed Ex Packages use ZIP 20814)
Phone: 301-435-3047
Fax: 301-480-1066
romashks@nia.nih.gov


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