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.