Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05002062 |
| Other study ID # |
P.T.REC/012/003199 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 21, 2020 |
| Est. completion date |
June 7, 2021 |
Study information
| Verified date |
January 2022 |
| Source |
Cairo University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
There is a rising concern about quality of life of multiple sclerosis (MS) patients has
emerged. Cognitive dysfunction with primary fatigue and there correlation to the level of
disease inflammatory process has got great interest in MS research .
The aim of the present study was to examine the influence of using a computer-based cognitive
behavioral therapy on primary fatigue, cognitive dysfunction, and inflammatory biomarkers for
patients with MS.
Patients and methods A total of 40 MS patients (Expanded Disability Status Scale<5) were
divided into two groups, both groups are suffering cognitive decline (using RehaCom software
to assess attention/concentration, memory and reaction behavior) with primary fatigue
according to the Fatigue Severity Scale (FSS>36). Patients with depression and sleep problems
were excluded from the study. Patients in both groups have elevated serum levels of tumor
necrosis factor-α (TNF-α) and interferon-γ (IFN-γ).
Patients in (G1) underwent conventional physical therapy program for MS including aerobic
training, resistive training and a flexibility program, patients in (G2) underwent an
intensive computer-based cognitive program for attention, concentration, memory and reaction
behavior using the RehaCom software.
The conventional physical therapy interventions for both (G1) sustained for three months, 45
minutes to 1 hour, 3 times/week. The computer-based cognitive behavioral therapy for patients
in (G2) was prescribed as following (45 minutes to 1 hour a session, 3 times/week for
continues three months).
Description:
This study was done to to examine the influence of using a computer-based cognitive
behavioral therapy on primary fatigue, cognitive dysfunction, and inflammatory biomarkers for
patients with MS. This study was conducted in the time period between December 2020 till May
2021.
1. Subjects Selection:
Forty MS patients were selected from Neurology Department Faculty of Medicine, Cairo
University out-patient clinic , Multiple Sclerosis Research Unit, Cairo University and
from Faculty of Physical Therapy ,Cairo University out-patient clinic. The patients were
diagnosed and referred from a neurologist. All the patients were referred from a
neurologist as a clinically definite MS according to Mcdonald criteria. The diagnosis
was confirmed by MRI. The patients were assigned into two equal groups (Conventional
physical therapy program)(G1) & ( Computer-based cognitive behavioral therapy)(G2).
- Inclusion criteria:
- All types and representations of MS patients were included in this study. -
The age of the patients ranged from 20-45 years. - All the patients subjected
to a standard neurological examination before participating in the study(
sensory, motor, coordination , balance, gait and fundus examination).
- All the patients were free from any other neurological problems.
- Multiple sclerosis patients were subdivided into two equal groups
(Conventional physical therapy program)(G1) & ( Computer-based cognitive
behavioral therapy)(G2).
- All included patients for both groups complained from fatigue for more than
three months with total score of FSS ≥ 36.
- All included patients complained of a cognitive decline for more than three
months ( including attention, concentration or memory problems according to
the RehaCom scores)
- All the patients were ambulatory with mild to moderate disability according to
the expanded disability status scale (EDSS) ≤ 5(Ambulatory without aid or rest
for 200 meters).
- Serum levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were
elevated in all recruited patients for both groups.
- All the patients were medically stable with absent or mild hemiparetic,
ataxic, sensory or motor manifestations.
- The main complain for all patients in both groups is the sense of fatigue and
varying degrees of cognitive dysfunction.
- All recruited MS Patients kept on their medications as glucocorticoids,
amantadine , betaferon , hypnotics and modafinil throughout the study.
- All patients were educated .
- Exclusion criteria:
The patients were excluded when they met one of the following criteria:
- Severe visual, verbal or acoustic impairments that may interfere with cognition
testing,
- Serious chronic illness that could interfere with or modify assessment or treatment
outcomes.
- Low leukocyte count & elevated ESR as this interfere with cytokine levels.
- Secondary causes of fatigue including severe depression ( beck depression inventory
(BDI ≥ 21) and sleep disturbance ( Epworth sleepiness scale (ESS ≥ 12)
- Inability to complete questionnaires study outcome measure as in severe cognitive
impairment and illiteracy.
- Magnetic resonance imaging (MRI) of the brain showed plaques within the cingulate
gyrus, insula , temporo-basal cortical areas or diffuse patchy frontal lesions as
they usually complain from cognitive impairment independent of fatigue.
2. Instrumentations & Procedures :
A. Assessment Interventions:
• Fatigue severity scale (FSS) : It is valid and reliable scale used to assess fatigue
severity in MS patients , and to distinguish fatigued MS patients from non fatigued MS
patients(Armutlu et al,2007). It is self reported questionnaire consisted of nine
sentences. A list of statements/questions is provided. These statements are related to
the different aspects of fatigue and how it affects the body.
Expanded Disability Status Scale (EDSS)was used to exclude patients with fatigue
secondary to moderate to severe disability. It provides a total score on a scale that
ranges from zero to ten. The first levels 1.0 to 4.5 indicate people with a high degree
of ambulatory ability. The subsequent levels 5.0 to 9.5 indicate loss of ambulatory
ability. Grade (Zero) indicate normal neurologic exam. Grade (Five) indicate the ability
of the patient to ambulate without aid or rest for 200 meter but disability is severe
enough to impair full daily activities. (Ten) indicate death due to MS.
Beck depression inventory scale (BDI) was used to exclude patients suffering from
fatigue secondary to depression. It composed of twenty one questions each with four
possible responses ranging from "zero to three". Each question assess a specific symptom
common among people with depression.
Epworth Sleepiness Scale (ESS)was used to exclude the patients suffering from fatigue
secondary to sleep disturbance. It assess daytime sleepiness in people with multiple
sclerosis . It consists of eight questions regarding sleep in different physiological
and psychological conditions in multiple sclerosis patients.
Rehacom Software to assess cognitive function : It is a computer-based intensive
cognitive rehabilitation test used to assess patient's cognitive functions. It includes
32 assessment tasks for attention, memory , logical reasoning& executive functioning. It
composes of regular PC , 1G RAM , DVD drive, 100 GB hard drive with windows XP SP3, 128
MB RAM direct 3D graphic card , Screen at least 19" , regular PC keyboard or Rehacom
panel & printer .The Rehacom software version is (patient enpult (1990-1997)
EN/ISO-13485-certified). It is characterized by easy handling, close to reality ,
motivating for patients.
Blood analysis: A blood sample was collected from each patient in both groups before and
after the 4 months treatment intervention. Assessment of patients on immunomodulatory
therapy was postponed 36 hours from the last dose. Serum blood samples were immediately
stored on ice. TNF-α and IFN- γ were measured using The Quantikine Human TNF-alpha &
IFN-gamma Immunoassay ELISA kit . It is a 3.5 or 4.5 hour solid phase ELISA designed to
measure human TNF-alpha & IFN-gamma in cell culture supernates, serum, and plasma. It
contains E. coli-derived recombinant human TNF-alpha, IFN-gamma and antibodies raised
against this protein and antibodies raised against the recombinant factor. It has been
shown to accurately quantities the recombinant factor
(http://www.rndsystems.com/Products/DIF57&sta00c/aqQ).
B. Treatment Interventions:
- Conventional Physical Therapy Program for patients in (G1):
Including (aerobic training 20 minutes, resistive training 15 minutes and flexibility
program for 15 minutes), total conventional PT session timing (45 to one hour), 3 times
/week for subsequent 3 months.
- Computer- based Cognitive training using Rehacom Software in addition to
Conventional Physical Therapy Program in (G2) :
Cognitive training including the attention/concentration, memory and reaction behavior
domains, The time of each cognitive training session(45 to one hour), 3 times /week for
consecutive 3 months.
- Each domain in the cognitive training tests consists of one hundred levels of
difficulty . Each level has an average 22 subtests. The maximum period of the
session was about (60 minutes) for each patient with five minutes rest in between
each level.
- In Rehacom cognitive training, each patient is trained according to his/her primary
cognitive level, which is predetermined during the assessment stage of the study.
3. Data Analysis and Statistical Design:
- All analyses were performed on SPSS for Windows version 22 (IBM Corp., Armonk, NY,
USA).
- At the baseline assessment, the mean values among the two groups were compared by
one-way ANOVA for independent samples for continuous data or chi squared for
categorical data.
- The effects of the treatment pre-intervention and immediately post intervention
were examined using the two factor ANOVA with factors 'time' (baseline, immediately
post treatment intervention) on FSS ,RehaCom Cognitive domains' scores (
attention/concentration, memory & reaction behavior), and serum levels data of
tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ).
- Data were expressed as mean ± standard deviation (SD), A p value less than 0.05 was
considered statistically significant.
