Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT01954823 |
| Other study ID # |
CMC-13-0065-CTIL |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
September 29, 2013 |
| Last updated |
August 2, 2015 |
| Start date |
September 2015 |
| Est. completion date |
December 2016 |
Study information
| Verified date |
August 2015 |
| Source |
Carmel Medical Center |
| Contact |
Ariel Miller, MD/PhD |
| Phone |
972-4-8250851 |
| Email |
Ariel Miller [@]netvision.net.il> |
| Is FDA regulated |
No |
| Health authority |
Israel: Ministry of Health |
| Study type |
Interventional
|
Clinical Trial Summary
Multiple Sclerosis (MS) is the most common chronic neurological disease affecting young
adults, with onset usually at the age 20-40. Disease modifying therapies are available to
MS, as well as drugs to improve patients' symptoms.
Choosing the optimized treatment for each patient is a challenge to neurologists since
predictive biomarkers for therapy are yet to be validated and approved. Current therapy
decisions are based predominantly on clinical evaluation of disability and disease relapses.
Adherence to treatment in MS is sub-optimal.
Over the past few years a growing involvement of patients in their healthcare is noted,
specially in chronic diseases, and Patient Reported Outcomes (PRO) are being incorporated as
part of therapy evaluation.
Several electronic patients diaries to track adherence to therapy, PRO and drugs side
effects in diseases such as epilepsy are available. A mobile interactive patient diary
(e-diary) tailored for persons with MS was developed. Users can enter data on drugs intake,
drugs-side effects and disease symptoms and receive reminders regarding adherence to
treatment.
The aim of this study is to assess the benefits of the use of an e-diary for MS patients on
healthcare. In order to achieve this goal, 80 MS patients will be randomized into two
groups: a study group with access to the e-diary and a control group. After a period of one
year, satisfaction with the e-diary will be assessed. The effect of the use of the e-diary
on quality of life, on clinical outcomes and on adherence to therapy will be evaluated by
comparing the two groups.
This study will indicate the possible contribution of an e-diary for the evaluation of drugs
safety and efficacy and of patient adherence to therapy, to be applied in clinical trials
and towards improvement of MS patient' care.
Description:
Multiple Sclerosis (MS) is the most common chronic neurological disease affecting young
adults, with onset usually at the age 20-40. Women are affected 3-4 times more than men. The
disease is characterized by 2 main phenotypes: relapsing-remitting or progressive course.
MS is a complex multi-factorial disease, with underlying both genetic and environmental
factors. Different populations have different susceptibility (Compston and Coles 2008).
Clinical disability is due to distraction of the Central Nervous System (CNS) myelin (mainly
oligodendrocytes) due to 3 processes (Franklin 2002; Franklin and Ffrench-Constant 2008;
Frischer, Bramow et al. 2009):
1. Inflammation- immune cells with aberrant activity invade the brain and spinal cord and
cause distraction of CNS myelin (process called demyelination and secondary
neurodegeneration - axonal and neuronal loss)
2. Primary neurodegeneration (axonal and neuronal loss) - without prominent inflammation
3. Repair - the inflammatory and neurodegenerative processes are followed by an attempt of
the CNS to repair - however, this partial and incomplete repair is often the basis of
residual deficits and disability (Chandran, Hunt et al. 2008) .
These processes cause damage of the CNS, brain and spinal cord, leading to deficiencies in
several neurologic systems such as motoric, sensory, sphincters, visual and cognitive.
MS is diagnosed by a clinical evaluation of the neurologist in conjunction with the
detection of inflammation in the white matter in the CNS through MRI.
Following the increased understanding of the disease, in the last 10-15 years there are new
subcutaneous injection immunotherapies available (COPAXON / TEVA; Interferon -beta: Avonex.
Betaferon and Rebif) and Tysabri infusion . These drugs can cause side effects at such an
extent that treatment may have to be discontinued. Recently an oral drug Gilenya was
released to the market, and additional oral drugs such as Laquinimod and BG-12 (Dimethyl
Fumarate) are at different phases of development. However these can attenuate the disease
(reduce the number of relapses per year) but cannot cure it. Also, they are beneficial in
only ~40 % of the Relapsing -Remitting patients. Currently there are no treatments for
patients with the Progressive Disease - who have gradual increased disability (Murray 2006).
Intravenous steroids are the short term treatment for acute relapses. In addition to the
long term immunomodulatory drugs, disease modifying drugs (DMD), there are also drugs used
to alleviate some of the MS symptoms, such as Provigil, for fatigue and Fampyra for
improvement of walking disabilities.
With the growing number of drugs available for the treatment of MS and its symptoms, the
evaluation of treatment success is essential so the best treatment can be fitted to each
individual. Presently, there are no objective tools for assessment of treatment efficiency.
MRI is an expensive procedure that does not add much information beyond the clinical exam.
CSF (cervical spine fluid) is an invasive and painful examination which can help in MS
diagnosis but is not related to disease course. Treatment evaluation is based mainly in two
parameters: disability (measured by EDSS) and annual relapse rate. Both measures have
disadvantages: 1) EDSS indicates mostly motorical disability and does not take into account
other implications of the disease, such as cognitive problems and fatigue, 2) the number of
relapses per year may differ among neurologists, since generally only relapses with
indication to steroids treatment are taken into consideration and steroids indication
variates among neurologists.
Over the past few years a growing involvement of patients in their healthcare can be noted.
Healthcare organizations recognize the importance of this involvement both because of an
increasing public demand and because patient involvement is being considered positive to the
health system, specially in chronic diseases.
Patient Reported Outcome-PRO can be defined as "evaluation of treatment success based on the
patient point of view". The patient grades the intensity of symptoms related to the disease
or side effects of the treatment and report his general well being with the help of measures
such as Health-Related Quality of Life (HRQoL). PRO can be an useful measure in treatment
evaluation for some reasons: First, patients today expect to know about drugs side effects
not only from the medical staff point of view but also from the view of other patients
taking the drug (Basch 2010). Secondly, one of the bigger challenges today in the management
of MS is treatment adherence. It has been shown that about 50% of the patients discontinue
disease modifying therapy before completing two years of treatment (Bruce and Lynch 2011).
PRO could contribute to the identification of the reasons for non-adherence allowing
interventions for adherence improvement.
The main difficulties for collecting PRO are: 1) the patient capability of relating to the
physician during an encounter all the relevant symptoms he had since the last visit, and 2)
the fact that the patient's report has to be compared to his adherence to therapy. Recently
the FDA, recognizing the importance of the use of PRO, has founded a consortium for
developing and evaluating PRO (Riazi 2006; Goldman 2010).
An electronic diary (e-diary) tailored for persons with MS was developed. The diary is an
Internet application that can be used through the web or iphones. Data on medical history,
drugs intake, drugs side effects and disease symptoms (including intensity) can be entered
by the user. The application can produce graphs based on the data entered and send reminders
to the user's email or cellular phone. It can give the physician a complete insight on
patient adherence and on the outcomes according to the patient's view.
A similar diary for persons with epilepsy has been used by thousands of persons in the past
two years (https://my.epilepsy.com/irody/login-page.php) (Fisher 2010; Le 2011). In face of
the importance of patient involvement in medical decisions and since that are not objective
measures of treatment success in Multiple Sclerosis that can be used routinely, an
electronic diary can contribute to the evaluation of therapy, regarding both efficiency and
safety.
Aim(s)
The main aims of this study are to assess the contribution of the use of an e-diary by
people with MS on:
1. Adherence to therapy;
2. Quality of life and clinical outcomes; and
3. Collection of data on disease symptoms, treatment side-effects, and PRO and its
relevance for clinical decision making.
A second aim of this study is to assess the e-diary usability.
Research hypothesis Patient use of an electronic diary will contribute to patient adherence
to treatment and to clinical outcomes and will allow collection of reliable data on
symptoms, side effects and treatment outcome from the patient point of view.
Work plan outline:
MS Patients, visiting the Multiple Sclerosis Center at the Carmel Medical Center and being
treated by DMD or symptomatic drugs for MS will be invited to participate in this study.
After recruitment and signing an informed consent for the study, participants will be
randomized in two groups: the first one, the study group, will have access to a MS patients
e-diary during one year, and in parallel will continue to receive standard medical
follow-up. The second one, the control group, will receive standard medical care only.
Participants of both groups will be asked to fill questionnaires on demographic data,
quality of life and therapy adherence.
The e-diary allows data entry and retrieval through computers or iPhones. Users can enter
data on medications, medical visits, drugs side effects, receive reminders and produce
graphic and textual reports of the data entered. Participants will use the diary for one
year and details of the use will be automatically collected. In the end of this period,
clinical and personal data of each group on baseline and after one year and of the two
groups will be compared. Users' and medical team satisfaction of the e-diary will be
evaluated.
Study plan:
Number of participants: 100 MS patients.
MS patients will be recruited through the MS center clinic at Carmel Medical Center after
receiving an explanation from Prof. Miller, or the attending neurologist authorized by Prof
Miller to do so, on the study aims and protocol, and signing an informed consent, including
the release of Clalit Health Services from any responsibility regarding information
security. Participants will be randomized in two groups: the first one, the study group,
will have access to a MS patients e-diary during one year, and in parallel will continue to
receive standard medical follow-up. The second one, the control group, will receive standard
medical care only. Information regarding their personal and family medical history,
including data such as demographic and ethnicity data, data on smoking and dietary habits,
vitamins intake, other diseases, education and occupation will be collected from both groups
via the "Personal information questionnaire". Participants will also fill the MSTAQ
(Multiple Sclerosis Treatment Adherence Questionnaire) questionnaire on adherence to
treatment at baseline, after 6 months and one year, and the MSQoL-54 (Multiple Sclerosis
Quality of Life-54 Instrument) questionnaire on quality of life at baseline and after one
year. Medical staff will fill the "Clinical questionnaire" detailing patient clinical status
prior to the study and the Clinical Follow-up questionnaire" after 6 months and one year.
These questionnaires will be filled in printed forms during participants visits to the
clinic. When necessary, data will also be collected from medical records. Data collected
through participants and physician filled forms and from medical records will be stored on
an Excel or Access data base. In addition, data regarding the use of the diary will be
automatically collected.
Use of the electronic diary:
Participants in the study group will receive a code to access the e-diary through a computer
or an iPhone. Participants that don't have an I-phone may be granted one for the study
period. The data entered in the diary will be maintained in a secured Internet server and
will not include any identified data.
The diary can collect data on:
- Medical data: information on diseases, treatments and attending physicians
- Diary: daily report of drugs intake, symptoms and their intensity and additional
relevant data
- Reminders: the application can send reminders on drug intake or medical appointments to
cellular phones or emails
- Reports: textual and graphical reports of the data in the diary can be created The
e-diary was developed for patient use and data entered is not automatically accessed by
the medical staff. Patients will be instructed to bring the reports produced by the
diary to their medical appointments. In addition, patients will be instructed to
contact by phone the medical staff at the clinic in case they feel any change and/or
deterioration in their medical condition, as habitual in our clinic.Participants of the
study group will receive instructions on how to use the diary and technical assistance
will be available during the study. Follow-up on diary's use will take 1 year. The
medical follow-up of participants will be as usual in the MS center for both groups.
Data regarding the use of the diary will be collected directly from the application,
including:
- Number of entries
- Duration of entries
- Frequency and pattern of use
- Pages visited
- Time elapsed between a clinical event and report to the clinical staff
- Access by computer or Iphone
- Adherence to treatment
- Clinical related data Participants showing low/no access to the application will be
contacted by the medical team and will be encouraged to use the diary. These contacts
will be taken into consideration during statistical analysis.
After the follow-up period participants of the study group and the medical staff will fill
the "Questionnaire for Diary evaluation" regarding satisfaction from the tool. Medical staff
will fill the "Clinical follow-up questionnaire" for the two groups.
Data analysis
In the end of the follow-up period, data collected directly from the application and data
from the questionnaires will be analyzed as follows:
1) Adherence to treatment: In the study group, adherence to treatment will be assessed by
data registered on the e-diary and by questionnaires applied on baseline, after six months
and one year. In the control group, adherence to treatment will be assessed by
questionnaires only. Questionnaires from the two groups will be compared. In addition, the
study group questionnaire on adherence will be compared to data on adherence registered in
the e-diary . 2) Health-related quality of life and clinical outcomes: Clinical data such as
EDSS, number of relapses and hospitalizations will be collected by questionnaires completed
by the medical team. Quality of life will be assessed by questionnaires completed by the two
groups on baseline and after one year and the results will be compared. Since patients can
ask to visit the clinic or to call the medical team beyond regular follow-up if they feel
necessary, the number of these visits and calls in the two groups will be compared. 3) Data
captured in the e-diary: Data entered by the study group in the e-diary will be compared to
data entered in the Electronic Medical Record by the medical team during regular follow-up
of the control group. Data from both groups will be classified according to various
parameters such as: relating to efficacy or safety of therapy, physician response and
physical or emotional symptom. 4) E-diary usability: Adherence to the diary will be assessed
from data on the pattern of use of each participant. Satisfaction will be assessed through
questionnaires applied both to patients and to attending physicians.
Ethical issue:
Treatment will not be affected by participation in the study. Data collection and handling
will be coded to assure privacy of participants and will be handled by Prof. Ariel Miller
and his authorized staff. All the keys to the codes will be saved. Participants' regular
follow-up and visits to the clinic will continue.
Data management:
Data collected through participants and physician filled forms and from medical records will
be stored in an Excel or Access data base. The database is password protected, Prof Ariel
Miller, and his authorized staffs are responsible for its update and data verification.
Statistics:
The continuous variables will be presented by mean, median and standard deviation. The
categorical variables will be presented in percentages. Differences in demographic and
clinical characteristics between the study group and the control group will be assessed
using Chi square test for the categorical variables, Independent t-test or Mann Whitney, as
appropriate, for the continuous variables. Differences in each group separately between
baseline and after 1 year will be assessed using McNemar test for the categorical variables,
paired T-Test or Wilcoxon paired test, as appropriate, for the continuous variables. For
more than two time points, Friedman test will be used. Multivariate logistic regression will
be used to identify which variables are independently associated to an increase in
adherence.Values p<0.05 will be considered to be significant.
Timetable:
The proposed study is scheduled for two years. Follow-up on the use of the electronic diary
will take up to one year and afterwards the data will be analyzed.
