Plain English Summary
Background and study aims
End Stage Renal Disease (ESRD) is the complete or almost complete failure of the kidneys to function. Dialysis or kidney transplantation are the only treatments that can help patients with this condition. In addition, these patients need to take a range of medicines, such as for blood pressure control, anaemia, and bone and mineral management. Haemodialysis (HD) is the most common dialysis treatment, and usually involves lengthy out-patient treatment sessions three times a week, placing significant burdens on the patient and their family or carers. A small number of patients can administer dialysis at home. A large proportion of ESRD patients suffer from depression (about 20%) which impairs quality of life (QoL), reduces their capacity to manage their own medications, increases the risks of other illnesses, and reduces life expectancy. In addition, many ESRD patients also suffer from poor energy levels and tiredness, and we are interested in how these symptoms relate to depression. Effective treatments, both psychological and drug-based, exist for moderate to severe depression. Effective drugs include Selective Serotonin Reuptake Inhibitors (SSRIs). ESRD patients have unique medical and psychological pressures, and it is unclear whether a SSRI is helpful for this group of patients. There are a very small number of limited studies in patients with this condition, so we do not know whether a SSRI is effective, whether there may be additional side effects, or even whether ESRD patients with depression would wish to take additional medication, such as a SSRI. The aim of this study is to examine these issues to allow us to work out the practicability of undertaking a larger study to formally answer these questions.
Who can participate?
Adults aged 18 or over with ESRD and receiving haemodialysis.
What does the study involve?
The study is split into three phases. Phase one will evaluate the number of ESRD patients who are diagnosed with depression. Phase two will assess the feasibility of conducting a drug trial in this group of patients by assessing the number who take part and evaluating their outcomes including the safety of sertraline in ESRD patients. Phase three will explore the patient experience of participating in a trial and taking additional medication. Participants will be randomly allocated to receive either sertraline (a licensed SSRI) or a placebo (dummy) drug. They will remain on the study medication and followed up for 6 months.
What are the possible benefits and risks of participating?
Firstly, we will be able to tell you if you suffer from depression. Secondly, you will have the opportunity of joining the clinical trial. We cannot promise the trial will help you, but if you receive treatment with sertraline your mood may improve. You will have extra contacts with the nursing and medical staff including the psychiatrist throughout the study period of 6 months, who will monitor you carefully. You will be asked questions about your mood by the psychiatrist and by completing questionnaires. Occasionally these questions can be a bit upsetting so it is important to remember that you do not have to answer any questions you do not want to. We cannot promise the trial will help you. You will not know if you are taking sertraline or the placebo. This means that you could feel better but you could also feel worse and your depression may get worse.
Where is the study run from?
East and North Herts NHS Trust and the University of Hertfordshire (UK)
When is the study starting and how long is it expected to run for?
April 2013 to February 2015
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Prof. Ken Farrington
ken.farrington@nhs.net
Trial website
Contact information
Type
Scientific
Primary contact
Prof Ken Farrington
ORCID ID
Contact details
Renal Unit
Lister Hospital
Coreys Mill Lane
Stevenage
SG1 4AB
United Kingdom
-
ken.farrington@nhs.net
Additional identifiers
EudraCT number
2012-000547-27
ClinicalTrials.gov number
Protocol/serial number
14560
Study information
Scientific title
A pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis
Acronym
ASSertID (A Study of Sertraline in Dialysis) Phase 2
Study hypothesis
The main research question is to evaluate the feasibility of conducting a randomised, double-blind, placebo-controlled pilot trial in patients with End Stage Renal Disease and depression. The treatment under investigation is Sertraline, a licensed SSRI. The study is split into three phases. Phase one will evaluate the number of ESRD patients who score as depressed on the BDI-II and PHQ9, and fatigued on the SF-36 and MFI. Phase two will assess the feasibility of conducting a randomised drug trial in this group of patients, by measuring the number who take part and evaluating their outcomes as well as looking at the safety and drug exposure of Sertraline in ESRD. Phase three will explore the patient experience of participating in this trial.
Ethics approval
NRES Committee London - Bentham, 01/11/2012, ref: 12/LO/1554
Study design
Pilot double-blind parallel-group placebo-controlled randomised trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details provided in the Interventions field to request a patient information sheet
Condition
Topic: Mental Health, Renal disorders; Subtopic: Depression, Renal disorders; Disease: Depression
Intervention
The main research question is to evaluate the feasibility of conducting a randomised, double-blind, placebo-controlled trial in patients with ESRD and depression. The treatment under investigation is sertraline, a licensed SSRI. The study is split into three phases. Phase one will evaluate the number of ESRD patients who score as depressed on the Beck Depression Inventory. Phase two will assess the feasibility of conducting a randomised drug trial in this group of patients by assessing the number who take part and evaluating their outcomes including the safety and drug exposure of sertraline in ESRD patients. Phase three will explore the patient experience of participating in a trial and taking additional medication. This is a pilot study looking at running a phase IV, double-blind, placebo-controlled, randomised trial with two arms (sertraline hydrochloride versus placebo). A block randomisation on a web-based programme has been prepared by Norwich CTU. Patients will be starting on the study medication 50 mg orally per day for 2 months, with the option of stepping up to 100 mg orally for the remainder of the trial, if clinically indicated. Patients will remain on the study medication and followed up for 6 months.
Contact details for patient information sheet:
Dr Karin Friedli
Trial Manager
Centre for Lifespan and Chronic Illness Research
University of Hertfordshire
College Lane
Hatfield AL10 9AB
United Kingdom
k.friedli1@herts.ac.uk
Intervention type
Drug
Phase
Not Applicable
Drug names
Sertraline
Primary outcome measure
The primary outcome measures relate to the feasibility of conducting a large-scale randomised controlled trial. The aim is to characterise:
1. The proportion of eligible patients
2. The extent to which patients refuse to take part
3. The number who complete the study
Secondary outcome measures
The secondary aims are to assess the acceptability of and adherence to the study treatment, to assess how missing data biases the study outcomes, and to record the reported adverse events and safety of the study treatment in this group of patients
The analysis will estimate the variability in BDI, MFI, SF-36 energy/fatigue subscale, PHQ-9, MADRS, KDQoL and EQ5D scores.
Overall trial start date
15/04/2013
Overall trial end date
28/02/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Screening eligibility:
1.1. Patients with ESRD and receiving haemodialysis. They will have started dialysis at least 3 months ago and have continued to receive dialysis in the past 3 months prior to the invitation to take part in this study
1.2. Adults aged 18 or over
1.3. Patients who speak and read English sufficiently well to complete questionnaires
2. Trial eligibility:
2.1. Patients with a Beck Depression Inventory (BDI-II) of 16 or above
2.2. Patients who, according to the CI/PIs, have a prognosis of more than 1 year
2.3. Patients with a diagnosis of mild to moderate Major Depressive Disorder according to a Diagnostic and Statistical Manual of Mental Disorders (DSM) IV interview conducted by a research psychiatrist
2.4. Patients who score 18 or above on the Montgomery-Asberg Depression Scale (MADRS)
2.5. Patients who have the mental capacity to understand the trial and are able to give consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 30; UK Sample Size: 30
Participant exclusion criteria
1. Patients who are currently being or have been treated for depression and/or anxiety with any antidepressants in the last 3 months
2. Patients who are currently being or have been treated for depression and/or anxiety with a formal psychological therapy in the last 3 months
3. Patients who are awaiting a planned living donor transplant within the period of the trial
4. Patients who have less than 1 year survival prognosis according to the nephrologist
5. Patients for whom Sertraline is contraindicated by their existing drug regimen according to the Summary of Product Characteristics
6. Patients with hepatic impairment, whose serum level of alanine transaminase (ALT) is two times the upper limits of normal or higher
7. Patients who have hepatitis B or hepatitis C, HIV/AIDS, and/or Creutzfeldt-Jakob disease
8. Patients who are pregnant or of childbearing potential who are not using adequate contaception
9. Patients who are or have been involved in an intervention study in the last 3 months
10. Patients with impaired coagulation judged by an international normalised ratio (INR) greater than 1.3
11. Patients who are currently taking MAOIs or pimozide
12. Patients who are currently taking triptans, antipsychotics, dopamine antagonists, tramadol, linezolid and warfarin
13. Patients with a diagnosis of a severe Major Depressive Disorder
14. Patients at moderate to severe risk of self-harm according to the assessment of the study psychiatrist
15. Patients who score above 4 on item 10 on the MADRS
16. Patients who answer yes to question A3G on the Mini-International Neuropsychiatric Interview (MINI)
17. Patients who have other known psychiatric conditions, including substance misuse, psychosis, or personality disorder, dementia or panic disorder, with the exception of other anxiety disorders (for example GAD or OCD)
Recruitment start date
15/04/2013
Recruitment end date
28/02/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Lister Hospital
Stevenage
SG1 4AB
United Kingdom
Sponsor information
Organisation
East and North Herts NHS Trust (ENHT) (UK)
Sponsor details
Lister Hospital
Coreys Mill Lane
Stevenage
SG1 4AB
United Kingdom
-
Fiona.Smith@whht.nhs.uk
Sponsor type
University/education
Website
Organisation
University of Hertfordshire (UK)
Sponsor details
College Lane
Hatfield
AL10 9AB
United Kingdom
-
j.m.senior@herts.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
NIHR Research for Patient Benefit (RfPB) (UK); Grant Codes: PB-PG-0110-21073
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26503099
2017 results in: http://www.ncbi.nlm.nih.gov/pubmed/28126706
2017 results in: http://www.ncbi.nlm.nih.gov/pubmed/28762106