Methods.Subjects 30 women diagnosed with lipedema age 18-65 will be randomized to (1:1) to 8
weeks of exercise training og a control group. Exclusion criteria includes ongoing eating
disorders and/or orthopedic limitations for exercise training. A compliance with the
training program of 80% will also be set as a criterion for completing the study.
Participants will be recruited via social media, via physiotherapists, via posters at GPs
and via a user representative from the Norwegian Lymphedema and Lipedema Association
(NLLF). The master's students will obtain informed consent cf. GCP and the Health
Research Act. The potential participants will have at least one week to consider their
participation. If a research participant should be injured on the basis of something the
investigators ask them to do, NTNU will have the insurance responsibility. The
investigators will collect data on the type and stage of lipedema, when the participant
was diagnosed. The investigators will also collect data on which clinical aids they are
using and how often, e.g., compressions aids.
Intervention
- - Training protocol The women will be randomized (1:1) to 8 weeks of
supervised high-intensity interval training (HIIT) that is 4×4 min intervals at 85-95% of
maximal heart rate (HRmax) with 3-minute active breaks (~60 % HRmax) in between
intervals, twice a week) on treadmills at the NextMove core facility at NTNU or to a
control group.
All participants will be provided with a pulse watch to keep after the
study is completed. In addition, the participants will perform exercise once a week on
their own following the correct exercise intensity. Pool training will be recommended
based on potential benefits from compression. Body composition, blood pressure, VO2max
(maximal oxygen uptake), questionnaire data and blood samples will be measured/collected
before and after the exercise intervention. The participants will write a diary for their
physical activity using standardized templates from the NextMove core facility.
Maximal oxygen uptake (VO2max) VO2max will be measured during uphill treadmill walking or
running (Woodway PPS 55 Med, Munich, Germany), using ergospirometry (Jaeger, Oxycon pro,
Hoechberg, Germany / Meta Max II, Cortex, Leipzig, Germany) as described earlier.11 A
warm-up period for 10 min (~60% of HRmax) will precede the test. A levelling off of
oxygen uptake (VO2) despite increased work load and respiratory exchange ratio ≥1.05 will
be used as criteria for VO2max. HR will be measured continuously during the test (Polar,
Polar Electro, Kempele, Finland), to define HRmax.
Anthropometric measurements Body weight, body mass index and waist-to-hip ratio will be
measured. Body composition will be measured using InBody. For measurement of body
composition, the investigators will use an instrument called Inbody 720 (Body Analysis
AS). Inbody 720 provides weight, muscle mass, fat percentage, metabolism and mineral
status non-invasively by sending weak electrical signals through the body. The whole test
lasts just a few minutes. Before the analysis the participants should be fasten at least
two hours and should avoid strenuous exercise. The standard procedures at NextMove will
be used to measure the weight and height of participants. The height will be measured
without shoes or head wear, this must be done with equal weight on both legs. The
distance between the legs shall be a foot. The heels should be in the ground at full
stretch their legs. The height is measured with one decimal. The weight is measured
without heavy clothes and shoes, while the participants are standing still. It will be
drawn 0.5 kg for the remaining clothes. The weight is measured with one decimal. The
participants must stand upright for measuring of waist and hip circumference and a
regular exhaust measuring the circumference one cm over the navel. The waist
circumference is measured with no decimals.
Blood pressure Blood pressure will be measured while the patient is sitting down and have
been resting for at least five minutes in a quiet room. It will be measured by a trained
person, with a handheld sphygmomanometer (Tycos, 5098-02CB, USA). Blood pressure will be
measured at the same time of the day for each individual at pre- and post test. The first
reading will be discarded and the mean of the next three consecutive readings with a
coefficient of variation below 15% will be used in the study, with additional readings if
required. The sleeve should be placed at heart level and customized with the size of the
participants arm.
Pain and fatigue registration Visual analog scale (VAS), measured by means of a 0-100 mm,
for pain will be used to collect data on pain. VAS has been used in the social and
behavioral sciences to measure a variety of subjective phenomena. A VAS is a straight
line, whose end anchors indicate the extreme boundaries of the sensation, feeling, or
responses to be measured. For example a VAS to measure pain can be labeled "no pain" on
one end and "pain as bad as it could possibly be" on the other end. Subjects respond to
the VAS by placing a mark through the line at a position which best represents their
current perception of a given phenomenon between the labeled extremes. Although a VAS may
be horizontal or vertical and of any length deemed appropriate, its most common form is a
100 mm horizontal line. The VAS is scored by measuring the distance, usually in
millimeters, from one end of the scale to the subject's mark on the line. In the present
study, a score from 1-100 was used for measuring self reported total pain and fatigue.
LYMQOL (Lymphoedema Quality of Life) BEN and Brief Pain Inventory will be applied.
Quality of life questionnaires Short Form Health Survey-36 (SF-36) will be used to track
potential changes in quality of life. The SF-36 consists of eight scaled scores, which
are the weighted sums of the questions in their section. Each scale is directly
transformed into a 0-100 scale on the assumption that each question carries equal weight.
The eight sections are; vitality, physical functioning, bodily pain, general health
perceptions, physical role functioning, emotional role functioning, social role
functioning, and mental health.
Standard blood analyses Blood collection and blood analyses will be performed using
standard local procedures for the general biomarkers in clinical use and will be
performed in all participants at the pre- and post-test. Three 3ml EDTA-tubes and one 3ml
Li-heparin-tube will be collected and sent to clinical-chemical analyses at St.Olav's
hospital. Parameters to be analyzed includes e.g. glucose, HbA1C, triglycerides,
HDL-cholesterol, total cholesterol, serum ferritin and hs-CRP. An additional two tubes of
blood (serum and EDTA) will be collected for later explorative biomarker assays. These
blood samples will be centrifuged and aliquoted before freezing and storing in the
LipidEx-biobank. A test from the standard laboratory that is without normal range may
indicate a need for following up by a doctor, will be reported back to the participant as
soon as possible, thus they will be asked to contact their general practitioner. The
participants must fast at least three-hours before blood sampling. The time of last meal
time for participants will be recorded on the patient form.
ELISA for lipedema biomarkers The ELISA technique can detect an amount of a given
protein, antibody, or antigen in a sample. Explorative biomarkers outside clinical use
will be assayd by ELISA methods established at the local laboratories at the Department
of Circulation and Medical imaging. Potential biomarkers include TNFalpha, interleukines
as well as PF4/CXCL4.
NMR Lipidomics/metabolomics/inflammatomics To explore the beneficial effects of HIIT on
blood profile in these individuals, NMR (nuclear magnetic resonance) technology will be
applied to determine if changes occur on the 1) lipoprotein subfractions that cannot be
detected by measuring standard lipids, 2) changes occur in the metabolome and 3) changes
occur in the inflammatory status. Lipidomics is a recently developed research area that
apply different techniques to perform large-scale analyses of circulating lipids. NMR
lipidomics utilizes differences in lipoprotein composition, size and density to extract
information on lipoprotein subclasses. Several studies have demonstrated an association
between lipoprotein subfractions and future cardiovascular health. This suggest that more
refined analyses of lipoprotein subfractions may lead to further improvements in
monitoring cardiovascular health. Lipidomics technology has developed rapidly over the
past decade, to the point where clinical application now is possible.
Statistical power This is a pilot study, as there is very limited knowledge on exercise
as treatment for lipedema. That is, no variables are available for power calculations.
The investigators have chosen to set the number to 15 in each group to be able to account
for up to 20% drop-outs. With the limited time available during a Master's project, this
is a realistic target.
Data protection Patient information will be stored and handled in conformity with
Norwegian laws and regulations.
