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:
Assessment of ad libitum energy intake at baseline to calculate the
exact prescription of CR and/or physical activity during the
intervention period.
Measurement of the adaptation in energy expenditure in response to
the intervention.
Assessment of adherence to the prescribed intervention regimen for
groups and/or individuals at several time points over the course of the
intervention.
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 [email protected]
