Parkinson's DiseaseNCT02632279
Tryptophan Depletion in PD Patients Treated With STN DBS
A study testing Tryptophan (TRP) depletion, Stimulator ON and Stimulator OFF in people with Parkinson's Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this study is to assess the effect of tryptophan depletion on mood and behavior in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Tryptophan (TRP) depletion, Stimulator ON and Stimulator OFF
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2015to 15 Nov 2017
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- subjects must be mentally competent
- subjects must have undergone STN DBS surgery for PD symptomatology
Who cannot join
- head injury
- stroke
- currentl malignancy or infection
- neurological disorders other than PD
- psychoactive medication: specifically antidepressants and antipsychotics ( a stable dose of benzodiazepines will be allowed)
- clinically relevant cognitive decline, operationalized as a MMSE score < 24
- current psychiatric syptomatology, operationalized as a Hamilton Depression scale score > 16 or a score >2 on one of the MDS-UPDRS section I, items 1-6
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg
About this study
Official title: Tryptophan Depletion in Parkinson's Disease Patients Treated With Deep Brain Stimulation of the Subthalamic Nucleus: Effects on Mood and Motor Functions
The purpose of this study is to assess the effect of tryptophan depletion on mood and behavior in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN). By doing this, the investigators hope to be able to identify risk factors for and mechanisms underlying psychiatric side effects of STN DBS. The study will be an intervention study with a placebo controlled, randomized cross-over design.
Read the detailed description
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremor, rigidity and slowness of movement. In later stages of the disease, when pharmacological treatment becomes less efficient, deep brain stimulation (DBS) of the subthalamic nucleus (STN) becomes a treatment option. Although motor symptoms improve significantly by DBS, a number of operated patients experience severe side effects, mostly related to mood, cognition or behavior. These adverse effects are most likely mediated through the serotonin (5-HT) system. Additionally, a dysfunction of the 5-HT system is implied in the pathophysiology of PD. PD patients are therefore regarded as 'vulnerable' to experiencing mood, cognitive and emotional problems due to changes in 5-HT activity.
To elucidate whether STN DBS is indeed the trigger for psychiatric and cognitive problems to arise in the PD patient, the 5-HT levels in PD patients implanted with STN DBS will be manipulated. In order to do this, the investigators will make use of the tryptophan (TRP) depletion method, an established research paradigm. In TRP depletion, the brain is depleted of TRP, the precursor of 5-HT, which consequently leads to lowered 5-HT levels. In both the normal and 5-HT depleted condition, mood- and cognitive parameters of the PD patients both with the STN stimulation on (ON) and off (OFF) will be assessed.
The goal is to get more insight into the effects of STN DBS in PD patients with a 5-HT vulnerabililty and the effects on 5-HT related mood and cognitive behaviour. This way, possible risk factors for and mechanisms underlying psychiatric side effects of STN DBS can be identified. The study is an intervention study with a placebo controlled, randomized cross-over design.
- Conditions
- Parkinson's Disease
- Being tested
- Tryptophan (TRP) depletion, Placebo, Stimulator ON, Stimulator OFF
- Keywords
- Parkinson's disease, Deep Brain Stimulation, Subthalamic nucleus, Tryptophan depletion, Serotonin
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tryptophan (TRP) depletionDietary supplement
Also called TRP depleted
TRP depletion will be accomplished by administering a TRP-low amino acid protein drink containing 100 g of gelatin powder. The protein mixture consists of 18 amino acids. According to Dutch law, TRP is considered a food supplement and is not registered as a medicine.
PlaceboDietary supplement
The placebo treatment will consist of an identical amino acid protein drink containing 100 g of gelatin powder to which 1.21g TRP is added.
Stimulator ONDevice
Participants will be tested while their stimulator is turned ON
Stimulator OFFDevice
Participans will be tested while their stimulator is turned OFF
| Study group | Role | What they receive |
|---|---|---|
| TRP depleted | Experimental | TRP depleted protein drink Receives: Dietary Supplement: Tryptophan (TRP) depletion; Device: Stimulator ON; Device: Stimulator OFF |
| Placebo | Placebo comparator | Balanced protein drink (+1.21g of TRP) Receives: Dietary Supplement: Placebo; Device: Stimulator ON; Device: Stimulator OFF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mood
as assessed through the Profile of Mood States
Measured: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino acid mixture, and 5.5 hours after intake of the amino acid mixture
Secondary outcomes (3)
Motor scores
as assessed through the MDS-UPDRS
Measured: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture, and 5.5 hours after intake of the amino-acid mixture
Impulsivity
as assessed through a reaction time task
Measured: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture, and 5.5 hours after intake of the amino-acid mixture
Emotional Responsiveness
as assessed through the emotional responsiveness task
Measured: There will be 4 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2015 (estimated)
- Study startNov 2015
- Primary completionNov 2017
- Study completion15 Nov 2017
Why it stopped: * Insufficient rates of participant accrual * Effects in opposite direction of hypothesis * Study was not feasible
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Brain Foundation
- Responsible party
- Sponsor
- Investigators
- Yasin Temel, MD, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02632279
- Sponsor's protocol ID
- Tryptophan depletion in PD
- Status last verified
- Aug 2018
- First submitted
- 26 Nov 2015
- Last updated
- 22 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tryptophan Depletion in Parkinson's Disease Patients Treated With Deep Brain Stimulation of the Subthalamic Nucleus: Effects on Mood and Motor Functions
- ClinicalTrials.gov ID
- NCT02632279
- Acronym / sponsor ID
- Tryptophan depletion in PD
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, Deep Brain Stimulation, Subthalamic nucleus, Tryptophan depletion, Serotonin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: * Insufficient rates of participant accrual * Effects in opposite direction of hypothesis * Study was not feasible
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Netherlands Brain Foundation
- Study start
- Nov 2015
- Primary completion
- Nov 2017 (actual)
- Study completion
- 15 Nov 2017 (actual)
- First posted
- 16 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the effect of tryptophan depletion on mood and behavior in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN). By doing this, the investigators hope to be able to identify risk factors for and mechanisms underlying psychiatric side effects of STN DBS. The study will be an intervention study with a placebo controlled, randomized cross-over design.
Detailed description
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremor, rigidity and slowness of movement. In later stages of the disease, when pharmacological treatment becomes less efficient, deep brain stimulation (DBS) of the subthalamic nucleus (STN) becomes a treatment option. Although motor symptoms improve significantly by DBS, a number of operated patients experience severe side effects, mostly related to mood, cognition or behavior. These adverse effects are most likely mediated through the serotonin (5-HT) system. Additionally, a dysfunction of the 5-HT system is implied in the pathophysiology of PD. PD patients are therefore regarded as 'vulnerable' to experiencing mood, cognitive and emotional problems due to changes in 5-HT activity.
To elucidate whether STN DBS is indeed the trigger for psychiatric and cognitive problems to arise in the PD patient, the 5-HT levels in PD patients implanted with STN DBS will be manipulated. In order to do this, the investigators will make use of the tryptophan (TRP) depletion method, an established research paradigm. In TRP depletion, the brain is depleted of TRP, the precursor of 5-HT, which consequently leads to lowered 5-HT levels. In both the normal and 5-HT depleted condition, mood- and cognitive parameters of the PD patients both with the STN stimulation on (ON) and off (OFF) will be assessed.
The goal is to get more insight into the effects of STN DBS in PD patients with a 5-HT vulnerabililty and the effects on 5-HT related mood and cognitive behaviour. This way, possible risk factors for and mechanisms underlying psychiatric side effects of STN DBS can be identified. The study is an intervention study with a placebo controlled, randomized cross-over design.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TRP depleted | Experimental | Dietary Supplement: Tryptophan (TRP) depletion, Device: Stimulator ON, Device: Stimulator OFFTRP depleted protein drink |
| Placebo | Placebo comparator | Dietary Supplement: Placebo, Device: Stimulator ON, Device: Stimulator OFFBalanced protein drink (+1.21g of TRP) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- subjects must be mentally competent
- subjects must have undergone STN DBS surgery for PD symptomatology
Key exclusion criteria (7 listed)
- head injury
- stroke
- currentl malignancy or infection
- neurological disorders other than PD
- psychoactive medication: specifically antidepressants and antipsychotics ( a stable dose of benzodiazepines will be allowed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tryptophan (TRP) depletionAlso: TRP depletedTRP depletion will be accomplished by administering a TRP-low amino acid protein drink containing 100 g of gelatin powder. The protein mixture consists of 18 amino acids. According to Dutch law, TRP is considered a food supplement and is not registered as a medicine. | Dietary supplement | TRP depleted |
| PlaceboThe placebo treatment will consist of an identical amino acid protein drink containing 100 g of gelatin powder to which 1.21g TRP is added. | Dietary supplement | Placebo |
| Stimulator ONParticipants will be tested while their stimulator is turned ON | Device | Placebo, TRP depleted |
| Stimulator OFFParticipans will be tested while their stimulator is turned OFF | Device | Placebo, TRP depleted |
Primary outcome
Mood
Time frame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino acid mixture, and 5.5 hours after intake of the amino acid mixture
as assessed through the Profile of Mood States
3 secondary outcomes
Motor scores
Time frame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture, and 5.5 hours after intake of the amino-acid mixture
Impulsivity
Time frame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture, and 5.5 hours after intake of the amino-acid mixture
Emotional Responsiveness
Time frame: There will be 4 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture
Results and safety
The study was stopped early (reason given: * Insufficient rates of participant accrual * Effects in opposite direction of hypothesis * Study was not feasible). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yasin Temel, MD, PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tryptophan (TRP) depletion, Stimulator ON and Stimulator OFF in people with Parkinson's Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
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 2 inclusion and 7 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: stopped early, as of the sponsor's last update on 22 Aug 2018. 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 Netherlands. 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 stopped early (reason given: * Insufficient rates of participant accrual * Effects in opposite direction of hypothesis * Study was not feasible). Results are not available in the source record.
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?
Mood (time frame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino acid mixture, and 5.5 hours after intake of the amino acid mixture). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Aug 2018.