Graded Exposure in patients with Painful Diabetic Neuropathy

Painful Diabetic Neuropathy (PDN) affects up to 20% of the people with diabetes
and is associated with considerable morbidity, mortality and diminished health
related quality of life (QOL). Unfortunately, pain treatment in PDN is
frequently not or only partially successful. Patients with PDN often suffer
from enhanced levels of anxiety, fears, and other negative feelings, such as
depression, as well as loss of mobility and unsteadiness, resulting in further
social isolation. Recent qualitative research confirms the existence of various
fears and beliefs that can contribute to diminished physical activity, mobility
and QOL. We propose an explanatory model for disability in PDN that states that
fear of falling and fear of hypoglycaemia both have a disruptive and negative
effect on physical functioning in patients with PDN. Avoidance of physical
activity can be a result of these fears, which may further lead to disability,
depression and overall lower QOL. In addition, suboptimal glycaemic control can
further influence the experience of pain by leading to hypervigilance.
Especially in patients with irrational and incorrect cognitions, fear will have
a disabling effect. Several pain populations, in whom fear indeed lead to
disability, have been treated successfully with graded exposure in vivo,
targeting fear of movement/pain, with an increase in physical activity and QOL.

To investigate the effects of the cognitive behavioural intervention GEXP on
physical activity and quality of life, hereby targeting specific fears in
patients with PDN.

Hypothesis: GEXP, as addition to usual care, increases the levels of physical
activity, thereby optimizing glucose regulation, reduce pain and disability and
increase QOL.

Novelty and importance of this work: So far studies have mainly concentrated on
conservative treatment methods for PDN. This project has a unique
multidimensional approach on disability in PDN. It includes a combination of
methods from psychological and medical sciences that cover a bio-psychosocial
perspective on pain related disability. The studies as proposed in the project
contain methods derived from research in medicine, movement sciences and
psychology. The results of the project will improve our understanding of
disability in patients with PDN. In case of proven effectiveness of the
proposed treatment program, the project will improve quality of life of
patients with PDN and can improve the care of DM in the Netherlands and abroad.

This study will be performed in a randomized replicated sequential single-case
experimental ABC-design with multiple measurements. After a > 3-week
no-treatment baseline measurement period (period A) patients are randomly
assigned to the treatment (GEXP; period B). The starting point of the
interventions will be determined at random by a computer system providing
allocations in a locked, unreadable file that will be assessed only by an
independent research administrator. At 6-months after baseline there will be a
follow-up period of 2 weeks (FU; period C) (Figure 2). Each outcome variable
will be measured systematically over time in each phase and on at least twenty
percent of the data points in each condition (periods A, B and C). The study
will include at least three attempts to demonstrate an intervention effect at
three different points in time.

Graded Exposure in vivo (GEXP) is a second-generation cognitive-behavioural
intervention, and is characterized by systematic and repeated exposure to
feared movements, activities and/or sensations in order to activate fear. The
GEXP that was developed for patients with chronic pain who report substantial
pain-related fear, and fear of movement/(re)injury in particular, is highly
structured, protocolled, individually tailored, and aims to restore a normal
pattern of daily function.
After a > 3-week no-treatment baseline measurement period (period A) patients
are randomly assigned to the treatment (GEXP; period B). At 6-months after
baseline there will be a follow-up period of 2 weeks (FU; period C).

Period A (>3 weeks):
• 1x blood sample.
• 1x questionnaires.
• 10 days of accelerometry.
• Daily registration in diary.

Intervention: GEXP during 8 weeks
• 1x blood sample.
• 2x 1 hour therapy, during 8 weeks.
• 8 weeks digital diary.
• 10 days of accelerometry.
• 2x questionnaire.
• 1x blood sample.

Follow-up:
• 1x blood sample..
• 1x questionnaire
• 2 digital diary,
• 10 days of accelerometry.

Graded Exposure in vivo (GEXP) is a second generation cognitive-behavioural
intervention in which fearful activities are being challenged. It is expected
that the risks associated with participation to the study are negligible and
that the burden will be minimal. The measurements that will be conducted during
the study consist of questionnaires and are not invasive or risk full.
In this study, blood samples at T1, T2, T3 and T4. Blood sampling itself can
cause bruises. Infections or continued bleeding are very rare.
Diabetes Mellitus type II is a disease that can adverse events such as muscle
injuries or periods of hypoglycaemia. The entire research team including
therapists, will be trained to recognize DM related complications and to know
which further actions are required.
In the case that an adverse event occurs, there is always a physician available
for consultation. All adverse events reported spontaneously by the subject or
observed by the investigator or his staff will be recorded.