Multiple n-of-1 self-investigation observational studies with patient-chosen products targeting the gut ecosystem to reduce chronic fatigue

Fatigue is commonly reported by many patients suffering from different chronic
(immune) disorders and reduces quality of life of these patients to a large
degree. Fatigue is regarded the result of a patient-specific complex interplay
of psychosocial, lifestyle and biological (e.g., immunological) factors, and
the effects of current treatment options are considered suboptimal. Current
needs of these patients are therefore unmet and alternative avenues to improve
patient quality of life are desirable. Starting point for the current study is
a direct link that has been found between the gut ecosystem (the gut microbiota
in interaction with host immune characteristics) and chronic fatigue. We focus
on fatigue in patients with a chronic (immune) disorder. For these patients,
the gut ecosystem is an interesting and relevant therapeutic target with the
expectation that manipulation of the gut microbiota and improving barrier
function may help to alleviate chronic fatigue.
Because of large interpersonal variation in gut microbiota, manipulating the
gut ecosystem is believed to have different effects in individual patients.
Therefore, effectiveness of manipulating the gut ecosystem on chronic fatigue
is preferably studied with a n-of-1 study approach (i.e., an idiographic
approach). This approach also addresses the strong desire of patients suffering
from chronic fatigue to self-investigate self-chosen products that may reduce
fatigue complaints in the context of their own daily life. The current
observational study will empower these patients to conduct self-investigation
of the individual effectiveness of self-chosen products targeting the gut
ecosystem. This study further involves a general practitioner (GP)-supported
infrastructure for data collection, data analysis and interpretation, and data
sharing.
In addition to idiographic analyses, a multiple n-of-1 approach also allows
statistical analyses at the group level (i.e., testing the mean effect on
fatigue across-subjects, denoted as a nomothetic approach). This approach will
help to answer the question whether or not the use of self-chosen products
targeting the gut ecosystem helps to reduce fatigue complaints across subjects.
In the current study, analysis across subjects also involves analyses of scores
of validated questionnaires and of pre-defined biological markers that are
regarded indices of possible predictive or mediating factors of chronic
fatigue. Finding (1) a mean effect across subjects during use of self-chosen
products targeting the gut ecosystem on the scores of validated questionnaires
and biological markers, and (2) an association between individual differences
in reduction of fatigue and changes in specified biological markers, might
indicate involvement of a biological mechanism.

The objective of this study is: (1a) to investigate the individual perceived
effectiveness of a self-chosen product targeting the gut ecosystem with the
assumption that this may reduce fatigue in the individual patient with a
chronic (immune) disorder, (1b) to assess the effectiveness of the use of
products targeting the gut ecosystem on fatigue in patients with chronic
(immune) disorder as a group, and (1c) to determine (across subjects) to what
extent a reduction in fatigue can be associated with changes in biological
markers that are hypothesized to have mechanistic relevance.

Multiple n-of-1 self-investigation observational studies with patient-chosen
products.

The burden placed upon the patient by this study is that s/he adheres to a
standardized measurements protocol during a 4 weeks baseline period, 8 weeks of
using the self-chosen product, and 4 weeks wash-out. In this protocol, patients
are asked to complete the intake questionnaire online, to complete a set of
validated questionnaires online for four times, and to complete the web-based
dietary recall tool three times. Patients are further enrolled in Ecologic
Momentary Assessment (EMA) for tracking of their symptoms. EMA is a methodology
with high-frequency assessment (i.e., several times per day) using the mobile
phone. EMA provides real-time, ecologically valid (i.e. applicable in actual
daily life) data in a minimally invasive or burdensome manner, taking less than
a minute per assessment. This involves a small set of standard EMA questions
that apply to all participants (e.g., fatigue) and several self-selected
questions on symptoms or lifestyle factors that a patient hopes the product is
helpful for. EMA produces intensive longitudinal idiographic data. Based on the
results of single subject time series analysis, each patient will be able to
evaluate a reduction in symptoms during the use of a self-chosen product. EMA
starts immediately after intake and informed consent and continues during the
baseline, product use, and wash-out. The patient receives personal EMA app
results a few weeks afterwards. Finally, blood, saliva, and feces samples are
provided by the patients at the start and end of baseline and at the end of
product use.
Risks are considered minimal; except for blood draws, all assessments are
non-invasive, and involves monitoring the perceived benefits of using food
supplements that are approved for general use. Blood draws will be conducted by
certified personnel. The assessment and data storage protocol is audited by the
data safety officer of the AMC and the Clinical Research Unit (CRU) of
Amsterdam UMC.
Patients benefit from participation in this study because it will provide
detailed and standardized information on the perceived benefit of product use
for de individual patient. In additional benefit is provided by the fact that
data sharing will inform other patients on effects and benefits (or lack
thereof) of a particular product. Further, post-hoc analyses of the data made
available through self-analyses may improve product choice and development to
better target the needs of the individual patient.