Pompe & Pain - Study to Assess Nociceptive Pain in Adult Patients With Pompe Disease

Summary

The primary aim of this nationwide, explorative, cross-sectional study in Germany is to characterize the prevalence, severity and quality of musculoskeletal pain in adult patients with late-onset Pompe disease (LOPD). The secondary objectives are to evaluate whether muscle pain is associated with muscle function, to assess whether muscle pain is associated with alterations of muscle tissue, and whether vitamin D metabolism and polymorphisms of ACE and ACTN3 genes may contribute to an increased level of perceived musculoskeletal pain. In a second step, exome sequencing of genes associated with musculoskeletal pain will be analyzed. Results of LOPD patients will be compared to patients with neuromuscular disorders with a similar distribution of muscle weakness and/or musculoskeletal pain.

Conditions

• Pompe Disease (Late-onset)
• Inclusion Body Myositis
• Spinal Muscular Atrophy Type 3
• FSHD

Interventions

DIAGNOSTIC_TEST

Beck depression inventory fast screen (Questionnaire)

Beck depression inventory fast screen questionnaire to detect severe depression for eligibility.

DIAGNOSTIC_TEST

Brief Pain Inventory (BPI) (Questionnaire)

Validated questionnaire for pain.

DIAGNOSTIC_TEST

German Pain Inventory (Questionnaire)

German Pain Inventory questionnaire for evaluation of pain. Module A, abbreviated questions of module S (sociodemographic questions S1, S2, S3, S4, S5 and S8) and module L (quality of life) and V (therapies) will be used.

DIAGNOSTIC_TEST

Fatigue Severity and Disability Scale (FSS) (Questionnaire)

Validated questionnaire for perceived fatigue

DIAGNOSTIC_TEST

Rotterdam Handicap Scale (RHS) (Questionnaire)

validated questionnaire to assess a patient's functional ability and level of handicap

DIAGNOSTIC_TEST

R-PAct (Questionnaire)

The R-PAct scale is designed specifically for Pompe disease, which consists of 18 items addressing daily life activities with three response options.

DIAGNOSTIC_TEST

Quick Motor Function Test

An evaluator observes the performance of a patient and scores the items separately on a 5-point ordinal scale (ranging from 0 to 4). A total score is obtained by adding the scores of all items and ranges between 0 and 64 points.

DIAGNOSTIC_TEST

Handheld Dynamometry (HHD)

To ensure a high level of objective measurement, muscle strength will also be assessed by handheld dynamometry. The following muscle groups will be tested: Arm abduction, elbow flexion, elbow extension, hip flexion, hip extension, knee extension, knee flexion, foot extension, foot flexion.

DIAGNOSTIC_TEST

Six-minute walk test (6MWT)

It is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. If a six-minute-walk-test was performed within the last 3 months within the routine treatment, no additional test will be performed and the distance walked in meters as well as borg scale will be recorded in the study CRF, including the date of the assessment. If not performed within the last six months, a six-minute-walk test will be performed once.

DIAGNOSTIC_TEST

Pressure pain threshold

For diagnosis of myofascial pain, pressure algometers are designed and conventionally used to measure deep pressure pain thresholds or tenderness resistance (Park, Kim et al. 2011), and the reliability of pressure pain thresholds according to raters or measurement frequencies has been proven to be relatively high (Chung, Um et al. 1992). The threshold is then determined as the arithmetic mean of the 3 series (in kPa). The measurement will be stopped immediately as the patient feels sensations of "burning", "stinging", "drilling" or "aching. Pressure algometry measurements will be performed on the trapezius, deltoid and supraspinatus muscles, the rectus femoris muscles, and the tibialis anterior muscles.

DIAGNOSTIC_TEST

Muscle ultrasound

Muscle ultrasound is an ideal imaging modality that allows for atraumatic, noninvasive, radiation-free point-of-care neuromuscular imaging. Muscular diseases are typically associated with an increase in the echogenicity from the muscle substance, distal attenuation of muscle echo and a corresponding loss of bone echo. A measurement on both sides deltoid, biceps and triceps brachii muscle, quadriceps femoris muscle, tibialis anterior muscle, rectus abdominis muscle and paravertebral muscles of cervical (C5-7), thoracic (Th4-6) and lumbar (L4-5) muscles. Muscle tissue alterations will be classified using the Heckmatt scale I-IV, describing muscle echogenicity. For muscle ultrasound, a linear 17MHz probe will be used. The muscle ultrasound assessment usually takes 15-20 minutes.

DIAGNOSTIC_TEST

Vital signs

Vital signs (blood pressure, heart rate, respiratory rate) will be measured before and after the six-Minute-Walk-Test (6MWT).

DIAGNOSTIC_TEST

Borg Scale

The Borg scale will be assessed, which is a self-reported questionnaire designed to subjectively assess dyspnea and exertion during activity (Borg 1982). The Borg scale rates dyspnea on a scale of 0 to 10 incorporating nonlinear spacing of verbal descriptors of the level of intensity of dyspnea. A higher Borg score indicates more severe dyspnea. The Borg scale will be administered before starting the 6MWT (≤ 5 minutes) and after completing the 6MWT (≤ 5 minutes).

DIAGNOSTIC_TEST

Laboratory assessment: Creatine kinase

CK-Level assessment in peripheral blood (peripheral venous blood draw)

DIAGNOSTIC_TEST

Laboratory assessment: Vitamin D Level

Vitamin D Level in peripheral blood (peripheral venous blood draw)

DIAGNOSTIC_TEST

Laboratory assessment: calcium

calcium level in peripheral blood (peripheral venous blood draw)

DIAGNOSTIC_TEST

Laboratory assessment: magnesium

magnesium level in peripheral blood (peripheral venous blood draw)

DIAGNOSTIC_TEST

Laboratory assessment: phosphate

phosphate level in peripheral blood (peripheral venous blood draw)

GENETIC

Genetic test: ACE polymorphism

peripheral venous blood draw for genetic analysis of ACE polymorphism

GENETIC

Genetic test: ACTN3 polymorphism

peripheral venous blood draw for genetic analysis of ACTN3 polymorphism

GENETIC

Blood draw for optional genetic exome sequencing

Optionally, upon additional informed consent, exome sequencing from peripheral blood will be performed in a second step to assess whether polymorphisms or pathogenic mutations in genes that are associated with chronic pain syndromes contribute to increased pain. This analysis will be performed collectively after enrollment is complete by the Genetikum Neu-Ulm. The selection of the genes is based on the Human Phenotype Ontology (HPO) search terms "myalgia", "muscle pain", "chronic pain", "musculoskeletal pain", "pain", and "nociceptive pain".

Sponsors & Collaborators

• LMU Klinikum

  lead OTHER

Principal Investigators

• Stephan Wenninger, PD Dr. med. · Study Principal Investigator

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-31

Primary Completion

2024-05-30

Completion

2024-09-03

Countries

• Germany

Study Locations