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Post-stroke DepressionNCT03761303

rTMS as an add-on Therapy in Patients With Post-stroke Depression

A study testing active rTMS in people with Post-stroke Depression, run by BDH-Klinik Hessisch Oldendorf at 1 site in Germany.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

About 50% of all stroke patients develop post-stroke depression (PSD). A meta-analysis has shown that rTMS treatment can reduce depressive symptoms in PSD patients. In addition to rTMS alone for the improvement of depression, the question arises as to whether a combination therapy of rTMS plus antidepressant… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Post-stroke Depression
What is being tested?
active rTMS
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteGermany
Study dates
1 May 2018to 1 Nov 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • first insult
  • Post-stroke Depression (17 item version of the Hamilton Depression Rating Scale [HAM-D]> 18 points)
  • capacity to consent

Who cannot join

  • insufficient cardiorespiratory stability
  • previous depression or previous use of antidepressants
  • pre-stroke psychological illnesses (eg psychosis, bipolar disorder)
  • severe cognitive impairment
  • aphasia
  • lefthanded
Show all 16Show fewer
  • decreased seizure threshold or history of epileptic seizures
  • taking medicines that lower the seizure threshold (local anesthetics, cortisone, alcohol, neuroleptics)
  • hemorrhages and cerebral edema (e.g., subarachnoid haemorrhage, intracerebral hemorrhage, subdural hematoma, epidural hematoma)
  • fresh and healed head wounds near the area to be stimulated
  • missing bone cover (relief spread)
  • colonization with a germ requiring isolation (e.g., MRSA, 3MRGN, 4MRGN)
  • recent myocardial infarction or higher grade cardiac arrhythmias
  • contraindications to rTMS: Metallic or magnetic implants containing iron, cobalt or nickel (e.g., pacemakers, brain pacemakers, automatic insulin pumps, electrodes, plates, clips, implanted hearing aids, dental implants, metal endoprostheses, metal parts, or metal fragments in the body).
  • pregnancy
  • no consent for study participation by the patient

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Institute for rehabilitative Research, BDH-Clinic Hessich Oldendorf

    Hessisch Oldendorf, Lower Saxony, 31840

Other trials in Germany

About this study

Official title: Investigation of the Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) as an add-on Therapy in Patients With Post-stroke Depression (PSD)

About 50% of all stroke patients develop post-stroke depression (PSD). A meta-analysis has shown that rTMS treatment can reduce depressive symptoms in PSD patients. In addition to rTMS alone for the improvement of depression, the question arises as to whether a combination therapy of rTMS plus antidepressant medication can achieve a stronger or longer-term effect in PSD patients. Unfortunately, there are currently no trials of combination therapy with rTMS and drug therapy in PSD patients. Therefore, this study will investigate whether combination therapy of antidepressant and rTMS can provide additional relief of depressive symptoms compared to antidepressant and sham rTMS therapy. It is assumed that the additional active rTMS achieves a faster normalization of affect and drive than with a sham rTMS, so that the patients benefit from neurorehabilitation measures earlier and more sustainably.

Read the detailed description

Depression is one of the most common forms of mental illness. According to studies by the World Health Organization (WHO), the World Bank and the European Brain Council [1], depression is the leading disease in Europe and Germany since the early 1990s.

Besides drug or psychotherapeutic treatment, repetitive transcranial magnetic stimulation (rTMS) is currently being used as a new non-invasive therapy for depression. The rTMS applies an electromagnetic coil to the patient's head, creating a magnetic field. Impulses emanating from the coil trigger a multitude of reactions at the point of stimulation which, for example, can alter the metabolism, lead to a release of neurotransmitters and a change in gene expression [2-3]. Pulses with a frequency ≤1Hz lead to a reduction of the excitability of the neurons and to an inhibition of cortical activity. In contrast, frequencies ≥5 Hz increase the excitability of neurons and increase cortical activity [4-5].

A large number of studies has already shown that rTMS in depressive patients leads to an improvement in depressive symptoms and has been shown to have an antidepressant effect [6]. In the United States, rTMS has been approved by the Food and Drug Administration (FDA) since 2008 as a treatment for patients with depression who do not respond to antidepressant drug therapy. The FDA recommends a high-frequency (10Hz) rTMS on the left dorsolateral prefrontal cortex (DLPFC) five days a week for four to six weeks [7]. The stimulation of the DLPFC is based on the valence hypothesis that the right hemisphere specializes in the processing of negative emotions and the left hemisphere is specialized in the processing of positive emotions [8] and the DLPFC controls emotional processing [9-10]. Activation of the left DLPFC is therefore associated with the processing of positive emotions [11].

About 50% of all stroke patients develop post-stroke depression (PSD) [12]. A meta-analysis has shown that rTMS treatment can reduce depressive symptoms in PSD patients [13]. In addition to rTMS alone, it is unkown if a combination therapy of rTMS plus antidepressant medication can achieve a stronger or longer-term antidepressive effect in PSD patients. Unfortunately, there are currently no trials of combination therapy with rTMS and drug therapy in PSD patients. Previous studies with depressive patients provide both results that suggest an additional effect of combination therapy [14-19] and results that found no difference between drug-only therapy and combination with rTMS [20-24]. The comparability of the studies is difficult due to the heterogeneity of the study designs. However, it is noticeable that a younger age (<50 years), an intervention duration of rTMS of four weeks, a higher dose of the antidepressant, an inter-train interval (interval between the trains) of <30 seconds and a total number of pulses of <1250 per day, associated with positive effects. However, further studies are needed that address the issue of an additional effect of combination therapy. In addition, a neurological disease was considered to be an exclusion criterion in some of the studies performed [14-15; 20; 23]. It is therefore questionable whether the study results can be transferred to PSD patients.

Therefore, this study will investigate whether combination therapy of antidepressant and rTMS can provide additional relief of depressive symptoms compared to antidepressant and sham rTMS therapy. It is assumed that the additional active rTMS achieves a faster normalization of affect and drive than with a sham rTMS, so that the patients benefit from neurorehabilitation measures earlier and more sustainably.

Being tested
active rTMS, sham rTMS
Keywords
rTMS, Escitalopram, add-on therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • active rTMSDevice

    The rTMS coil is applied tangentially to the head surface above the left DLPF (corresponding to position F3 of the international 10-20 system). For the stimulation intensity, the motor rest threshold of the patient is determined. The motor rest threshold is defined as the minimum intensity that triggers an EMG response with an amplitude> 50 μV in the first right interosseus dorsalis muscle in at least 5 out of 10 cases. The stimulation intensity within the rTMS therapy is 80 percent of the motor rest threshold. In one session, 1,000 pulses are applied in 10 trains at a frequency of 10 Hz (1 train = 100 pulses in 10 s). Between the individual trains there is an inter-train interval of 28 seconds. The total duration of a session is 5:52 minutes. In total, the patient recieve 20 sessions.

  • sham rTMSDevice

    Patients in the intervetion group (active rTMS stimulation) receive active 10 Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) over a period of 20 days, seven days a week (20 sessions).

Study groups in NCT03761303
Study groupRoleWhat they receive
active rTMSActive comparatorPatients in the intervetion group (active rTMS stimulation) receive active 10 Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) over a period of 20 days, seven days a week (20 sessions).
Receives: Device: active rTMS
sham rTMSSham comparatorPatients in the control group receive sham rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) over a period of 20 days, seven days a week (20 sessions).
Receives: Device: sham rTMS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes of Hamilton Depression Rating Scale [HAM-D; 17 Item Version]

    The primary endpoint is the change in the HAM-D score. A decrease of at least 50% from baseline on day 29 is considered clinically significant. From this, the responder rate is determined.

    Measured: For the clinical assessment of the severity of depression, the HAM-D is collected at the following times: day -7; baseline (day 1 before rTMS stimulation); day 2, day 8, day 15 and day 22).

Secondary outcomes (2)
  1. HAM-D score ≤8 Points

    A HAM-D score of ≤8 points is considered a decline in depression and is used to record the remission rate. It is expected that the decrease in the HAM-D from baseline (baseline) to the end of the study (day 22) in the active rTMS group is significantly greater than in the sham rTMS group.

    Measured: baseline (day 1 before rTMS stimulation); day 22

  2. HAM-D score (day -baseline)

    To analyze the long-term effect the HAM-D score will evaluated at day 36 (follow up). It is expected that the decrease in the HAM-D score from baseline to the follow-up (day 36) is significantly greater in the active rTMS group than in the sham rTMS group.

    Measured: baseline (day 1 before rTMS stimulation); day 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2018
  2. Study start1 May 2018
  3. Primary completion1 Nov 2021 (estimated)
  4. Study completion1 Nov 2022 (estimated)

Why it stopped: No eligible patients could be recruited.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
All patients will receive standard antidepressant therapy with 15 mg escitalopram (Selective Serotonin Reuptake Inhibitor) per day during the study. The dose of escitalopram is increased in all included patients from 5mg/day (day 1-3), over 10mg/day (day 4-6) to 15mg/day (from day 7). Patients in the experimental group (active rTMS stimulation) receive active 10 Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) over a period of 20 days, seven days a week (20 sessions). The comparison group receives a duration of equal long sham-stimulation. For transcranial magnetic stimulation, the Stimulator "PowerMAG Research 100" (Mag \& More, Munich, Germany) is used with a cooled double coil (PMD70-pCool).
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03761303
Sponsor's protocol ID
rTMS-PSD
Status last verified
Dec 2019
First submitted
30 Nov 2018
Last updated
17 Dec 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wittchen HU, Jacobi F. Size and burden of mental disorders in Europe--a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol. 2005 Aug;15(4):357-76. doi: 10.1016/j.euroneuro.2005.04.012.

    PubMed 15961293
  • Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet. 1985 May 11;1(8437):1106-7. doi: 10.1016/s0140-6736(85)92413-4. No abstract available.

    PubMed 2860322
  • Hausmann A, Weis C, Marksteiner J, Hinterhuber H, Humpel C. Chronic repetitive transcranial magnetic stimulation enhances c-fos in the parietal cortex and hippocampus. Brain Res Mol Brain Res. 2000 Mar 29;76(2):355-62. doi: 10.1016/s0169-328x(00)00024-3.

    PubMed 10762712
  • Mitchell PB, Loo CK. Transcranial magnetic stimulation for depression. Aust N Z J Psychiatry. 2006 May;40(5):406-13. doi: 10.1080/j.1440-1614.2006.01816.x.

    PubMed 16683966
  • Milev RV, Giacobbe P, Kennedy SH, Blumberger DM, Daskalakis ZJ, Downar J, Modirrousta M, Patry S, Vila-Rodriguez F, Lam RW, MacQueen GM, Parikh SV, Ravindran AV; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 4. Neurostimulation Treatments. Can J Psychiatry. 2016 Sep;61(9):561-75. doi: 10.1177/0706743716660033. Epub 2016 Aug 2.

    PubMed 27486154
  • Schutter DJ. Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis. Psychol Med. 2009 Jan;39(1):65-75. doi: 10.1017/S0033291708003462. Epub 2008 Apr 30.

    PubMed 18447962
  • Horvath JC, Mathews J, Demitrack MA, Pascual-Leone A. The NeuroStar TMS device: conducting the FDA approved protocol for treatment of depression. J Vis Exp. 2010 Nov 12;(45):2345. doi: 10.3791/2345.

    PubMed 21189465
  • Prete G, Laeng B, Fabri M, Foschi N, Tommasi L. Right hemisphere or valence hypothesis, or both? The processing of hybrid faces in the intact and callosotomized brain. Neuropsychologia. 2015 Feb;68:94-106. doi: 10.1016/j.neuropsychologia.2015.01.002. Epub 2015 Jan 7.

    PubMed 25575451
  • Brennan S, McLoughlin DM, O'Connell R, Bogue J, O'Connor S, McHugh C, Glennon M. Anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex enhances emotion recognition in depressed patients and controls. J Clin Exp Neuropsychol. 2017 May;39(4):384-395. doi: 10.1080/13803395.2016.1230595. Epub 2016 Sep 23.

    PubMed 27662113
  • Zilverstand A, Parvaz MA, Goldstein RZ. Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review. Neuroimage. 2017 May 1;151:105-116. doi: 10.1016/j.neuroimage.2016.06.009. Epub 2016 Jun 8.

    PubMed 27288319
  • Mondino M, Thiffault F, Fecteau S. Does non-invasive brain stimulation applied over the dorsolateral prefrontal cortex non-specifically influence mood and emotional processing in healthy individuals? Front Cell Neurosci. 2015 Oct 14;9:399. doi: 10.3389/fncel.2015.00399. eCollection 2015.

    PubMed 26528131
  • Aben I, Verhey F, Strik J, Lousberg R, Lodder J, Honig A. A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction. J Neurol Neurosurg Psychiatry. 2003 May;74(5):581-5. doi: 10.1136/jnnp.74.5.581.

    PubMed 12700297
  • Deng L, Sun X, Qiu S, Xiong Y, Li Y, Wang L, Wei Q, Wang D, Liu M. Interventions for management of post-stroke depression: A Bayesian network meta-analysis of 23 randomized controlled trials. Sci Rep. 2017 Nov 28;7(1):16466. doi: 10.1038/s41598-017-16663-0.

    PubMed 29184194
  • Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C, Myczkowski ML, Moreno RA, Marcolin MA. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biol Psychiatry. 2005 Jan 15;57(2):162-6. doi: 10.1016/j.biopsych.2004.10.029.

    PubMed 15652875
  • Rossini D, Magri L, Lucca A, Giordani S, Smeraldi E, Zanardi R. Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in patients with major depressive disorder? A double-blind, randomized, sham-controlled trial. J Clin Psychiatry. 2005 Dec;66(12):1569-75. doi: 10.4088/jcp.v66n1212.

    PubMed 16401159

Questions about this trial

What is this clinical trial studying?

A study testing active rTMS in people with Post-stroke Depression, run by BDH-Klinik Hessisch Oldendorf at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes of Hamilton Depression Rating Scale [HAM-D; 17 Item Version] (time frame: For the clinical assessment of the severity of depression, the HAM-D is collected at the following times: day -7; baseline (day 1 before rTMS stimulation); day 2, day 8, day 15 and day 22).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03761303, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.

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