Brain NeoplasmsPhase 4NCT02810899

Dexmedetomidine and Intelligence Development in Pediatric Patients Undergoing Craniotomy

A Phase 4 study testing dexmedetomidine and normal saline in people with Brain Neoplasms, run by Peking University First Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this randomized, double-blind and placebo-controlled pilot study is to investigate whether dexmedetomidine when used as an adjuvant to general anesthesia can decrease the harmful effects of anesthesia and surgery on intelligence development in pediatric patients undergoing craniotomy. Read more about this study

Who is it for?: Ages 2 to 12 years
Conditions the study is for: Brain Neoplasms
What is being tested?: dexmedetomidine and normal saline
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 60 participants
Where: 1 siteChina
Study dates: Sep 2015to Jun 2016
Phase: Phase 4
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 2 to 12 years
All sexes
No healthy volunteers
Child

Who may be able to join

Age of 2 years or older, but no more than 12 years;
Plan to undergo selective craniotomy under general anesthesia for intracranial tumor resection;
Written informed consent signed by legal guardians.

Who cannot join

Refused to participate by the legal guardians;
Body weight lower than the 3rd percentile or higher than 97th percentile of the normal body weight reference;
American Society of Anesthesiologists physical classification of IV or higher;
Unable to complete preoperative intelligence assessment because of coma, dysnoesia, or language barrier;
Diagnosed pulmonary disease (including acute respiratory tract infection) or cardiovascular disease (including congenital heart disease, hypertension, hypotension, bradycardia, atrioventricular block, or cardiac insufficiency);
Abnormal liver or renal function (liver enzyme or creatinine higher than 1.5 times of the upper normal limit;

Show all 9Show fewer

Other congenital diseases that may affect the development of the nervous system (such as Down's Syndrome);
Allergy to dexmedetomidine;
Other conditions that are considered unsuitable for study participation by the attending pediatricians or investigators.

Trial locations and contacts

1 site in 1 country.

China1 site

Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital
Beijing, Beijing Municipality, 100034

Other trials in China

About this study

Official title: The Effect of Dexmedetomidine as an Adjuvant to General Anesthesia on Intelligence Development in Pediatric Patients Undergoing Craniotomy: a Randomized, Double-blind and Placebo-controlled Pilot Trial

Read the detailed description

General anesthetics and sedatives are administered to millions of children each year to facilitate life-saving surgery and other essential surgical or medical procedures. In the past two decades, mounting evidence from animal and clinical studies have raised concerns that general anesthetics may produce harmful effects in the developing brain and lead to adverse neurodevelopmental outcomes. Factors that may influence the degree of injury include age at the time of drug exposure/surgery and cumulative anesthetic dose.

The Intelligence Quotients of pediatric patients with intracranial tumors are lower when compared with healthy children of same age. The investigators suppose that these patients are more sensitive to the neurotoxic effects of general anesthetics. Dexmedetomidine is an alpha 2-adrenoceptor agonist that provides sedation, anxiolysis, and analgesia, and has been shown to be safe to the brain in animal studies. In clinical studies, the use of dexmedetomidine decreases the consumption of anesthetics and opioids during general anesthesia and suppresses stress response induced by surgery. The investigators hypothesize that dexmedetomidine, when used as an adjuvant to general anesthesia, can reduce the neurotoxic effects of general anesthetics by decreasing anesthetic consumption and inhibiting stress response.

The purpose of this randomized, double-blind and placebo-controlled pilot study is to investigate whether dexmedetomidine, when used as an adjuvant to general anesthesia, can decrease the harmful effects of anesthesia and surgery on intelligence development of pediatric patients undergoing craniotomy.

Conditions: Brain Neoplasms
Being tested: dexmedetomidine, normal saline
Keywords: child, craniotomy, intelligence tests, dexmedetomidine, Disruption, Dehiscence, Mild Cognitive Disorder
Medical subject headings: Brain Neoplasms, Neurocognitive Disorders

What participants receive

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

dexmedetomidineDrug
Also called dexmedetomidine hydrochloride
A loading dose dexmedetomidine (0.5 ug/kg IV infused in 15 minutes) will be administered after anesthesia induction, followed by a continuous infusion at a rate of 0.5 ug/kg/h until the closure of the brain duramater at the end of surgery.
normal salineDrug
Also called 0.9% sodium chloride
Normal saline will be administered in the same rate, volume and duration as that in the dexmedetomidine group

Study groups in NCT02810899
Study group	Role	What they receive
Dexmedetomidine group	Experimental	A loading dose of dexmedetomidine (0.5 ug/kg IV infusion in 15 minutes) will be administered after induction of general anesthesia, followed by continuous infusion at a rate of 0.5 ug/kg/h until the closure of the duramater of the brain. Receives: Drug: dexmedetomidine
Control group	Placebo comparator	Normal saline will be administered in the same rate and volume as that in the dexmedetomidine group. Receives: Drug: normal saline

What is being measured

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

Intelligence Quotient
Tested with Chinese Binet Intelligence Scale
Measured: At 3 months after surgery

Secondary outcomes (4)

Time to anesthesia emergence
Measured: From end of surgery until reappearance of response to oral orders, assessed up to 24 hours
Time to extubation
Measured: From end of surgery until extubation, assessed up to 24 hours
Depth of sedation at the time of extubation
Assessed with Ramsay sedation scale
Measured: Immediately after extubation
Emergence agitation
Agitation will be assessed with anesthesia emergence agitation score.
Measured: From end of surgery until extubation, assessed up to 24 hours

Timeline

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

Sep 2015Jun 2016

First posted23 Jun 2016 (estimated)
Study startSep 2015
Primary completionFeb 2016
Study completionJun 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (11)Papers the sponsor has linked to this study.
Other trials for Brain NeoplasmsStudies of the same condition, open and under way.
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 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02810899
Sponsor's protocol ID: 2015[969]
Other IDs: ChiCTR-IPR-15007085
Status last verified: Sep 2016
First submitted: 8 Jun 2016
Last updated: 29 Sep 2016
Results posted: No
Data monitoring committee: Yes
Individual data sharing: Yes

Publications

Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. Anesthetic neurotoxicity--clinical implications of animal models. N Engl J Med. 2015 Feb 26;372(9):796-7. doi: 10.1056/NEJMp1414786.
PubMed 25714157
Cattano D, Young C, Straiko MM, Olney JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg. 2008 Jun;106(6):1712-4. doi: 10.1213/ane.0b013e318172ba0a.
PubMed 18499599
Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999 Jan 1;283(5398):70-4. doi: 10.1126/science.283.5398.70.
PubMed 9872743
Olney JW, Ishimaru MJ, Bittigau P, Ikonomidou C. Ethanol-induced apoptotic neurodegeneration in the developing brain. Apoptosis. 2000 Dec;5(6):515-21. doi: 10.1023/a:1009685428847.
PubMed 11303910
Jevtovic-Todorovic V, Absalom AR, Blomgren K, Brambrink A, Crosby G, Culley DJ, Fiskum G, Giffard RG, Herold KF, Loepke AW, Ma D, Orser BA, Planel E, Slikker W Jr, Soriano SG, Stratmann G, Vutskits L, Xie Z, Hemmings HC Jr. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth. 2013 Aug;111(2):143-51. doi: 10.1093/bja/aet177. Epub 2013 May 30.
PubMed 23722106
Poggi G, Liscio M, Galbiati S, Adduci A, Massimino M, Gandola L, Spreafico F, Clerici CA, Fossati-Bellani F, Sommovigo M, Castelli E. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages. Psychooncology. 2005 May;14(5):386-95. doi: 10.1002/pon.855.
PubMed 15386759
Hernandez MT, Sauerwein HC, Jambaque I, de Guise E, Lussier F, Lortie A, Dulac O, Lassonde M. Attention, memory, and behavioral adjustment in children with frontal lobe epilepsy. Epilepsy Behav. 2003 Oct;4(5):522-36. doi: 10.1016/j.yebeh.2003.07.014.
PubMed 14527495
Wang XW, Cao JB, Lv BS, Mi WD, Wang ZQ, Zhang C, Wang HL, Xu Z. Effect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta-analysis. Clin Exp Pharmacol Physiol. 2015 Aug;42(8):828-36. doi: 10.1111/1440-1681.12431.
PubMed 26016707
Li Y, Wang B, Zhang LL, He SF, Hu XW, Wong GT, Zhang Y. Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique. Anesth Analg. 2016 Apr;122(4):1202-10. doi: 10.1213/ANE.0000000000001165.
PubMed 26991622
Kim DJ, Kim SH, So KY, Jung KT. Effects of dexmedetomidine on smooth emergence from anaesthesia in elderly patients undergoing orthopaedic surgery. BMC Anesthesiol. 2015 Oct 7;15:139. doi: 10.1186/s12871-015-0127-4.
PubMed 26446479
Le Bot A, Michelet D, Hilly J, Maesani M, Dilly MP, Brasher C, Mantz J, Dahmani S. Efficacy of intraoperative dexmedetomidine compared with placebo for surgery in adults: a meta-analysis of published studies. Minerva Anestesiol. 2015 Oct;81(10):1105-17. Epub 2015 May 25.
PubMed 26005187

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Dexmedetomidine as an Adjuvant to General Anesthesia on Intelligence Development in Pediatric Patients Undergoing Craniotomy: a Randomized, Double-blind and Placebo-controlled Pilot Trial
ClinicalTrials.gov ID: NCT02810899
Acronym / sponsor ID: 2015[969]
Conditions: Brain Neoplasms
Keywords: child, craniotomy, intelligence tests, dexmedetomidine, Disruption, Dehiscence, Mild Cognitive Disorder
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Peking University First HospitalUniversity, hospital or other
Collaborators: Beijing Tiantan Hospital
Study start: Sep 2015
Primary completion: Feb 2016 (actual)
Study completion: Jun 2016 (actual)
First posted: 23 Jun 2016 (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.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Dexmedetomidine group	Experimental	Drug: dexmedetomidineA loading dose of dexmedetomidine (0.5 ug/kg IV infusion in 15 minutes) will be administered after induction of general anesthesia, followed by continuous infusion at a rate of 0.5 ug/kg/h until the closure of the duramater of the brain.
Control group	Placebo comparator	Drug: normal salineNormal saline will be administered in the same rate and volume as that in the dexmedetomidine group.

Who may qualify

Ages: 2 to 12 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

Age of 2 years or older, but no more than 12 years;
Plan to undergo selective craniotomy under general anesthesia for intracranial tumor resection;
Written informed consent signed by legal guardians.

Key exclusion criteria (9 listed)

Refused to participate by the legal guardians;
Body weight lower than the 3rd percentile or higher than 97th percentile of the normal body weight reference;
American Society of Anesthesiologists physical classification of IV or higher;
Unable to complete preoperative intelligence assessment because of coma, dysnoesia, or language barrier;
Diagnosed pulmonary disease (including acute respiratory tract infection) or cardiovascular disease (including congenital heart disease, hypertension, hypotension, bradycardia, atrioventricular block, or cardiac insufficiency);

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
dexmedetomidineAlso: dexmedetomidine hydrochlorideA loading dose dexmedetomidine (0.5 ug/kg IV infused in 15 minutes) will be administered after anesthesia induction, followed by a continuous infusion at a rate of 0.5 ug/kg/h until the closure of the brain duramater at the end of surgery.	Drug	Dexmedetomidine group
normal salineAlso: 0.9% sodium chlorideNormal saline will be administered in the same rate, volume and duration as that in the dexmedetomidine group	Drug	Control group

Primary outcome

Intelligence Quotient
Time frame: At 3 months after surgery
Tested with Chinese Binet Intelligence Scale

4 secondary outcomes

Time to anesthesia emergence
Time frame: From end of surgery until reappearance of response to oral orders, assessed up to 24 hours
Time to extubation
Time frame: From end of surgery until extubation, assessed up to 24 hours
Depth of sedation at the time of extubation
Time frame: Immediately after extubation
Emergence agitation
Time frame: From end of surgery until extubation, assessed up to 24 hours

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
Background: PubMed 25714157Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. Anesthetic neurotoxicity--clinical implications of animal models. N Engl J Med. 2015 Feb 26;372(9):796-7. doi: 10.1056/NEJMp1414786.
Background: PubMed 18499599Cattano D, Young C, Straiko MM, Olney JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg. 2008 Jun;106(6):1712-4. doi: 10.1213/ane.0b013e318172ba0a.
Background: PubMed 9872743Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999 Jan 1;283(5398):70-4. doi: 10.1126/science.283.5398.70.
Background: PubMed 11303910Olney JW, Ishimaru MJ, Bittigau P, Ikonomidou C. Ethanol-induced apoptotic neurodegeneration in the developing brain. Apoptosis. 2000 Dec;5(6):515-21. doi: 10.1023/a:1009685428847.
Background: PubMed 23722106Jevtovic-Todorovic V, Absalom AR, Blomgren K, Brambrink A, Crosby G, Culley DJ, Fiskum G, Giffard RG, Herold KF, Loepke AW, Ma D, Orser BA, Planel E, Slikker W Jr, Soriano SG, Stratmann G, Vutskits L, Xie Z, Hemmings HC Jr. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth. 2013 Aug;111(2):143-51. doi: 10.1093/bja/aet177. Epub 2013 May 30.
Background: PubMed 15386759Poggi G, Liscio M, Galbiati S, Adduci A, Massimino M, Gandola L, Spreafico F, Clerici CA, Fossati-Bellani F, Sommovigo M, Castelli E. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages. Psychooncology. 2005 May;14(5):386-95. doi: 10.1002/pon.855.
Background: PubMed 14527495Hernandez MT, Sauerwein HC, Jambaque I, de Guise E, Lussier F, Lortie A, Dulac O, Lassonde M. Attention, memory, and behavioral adjustment in children with frontal lobe epilepsy. Epilepsy Behav. 2003 Oct;4(5):522-36. doi: 10.1016/j.yebeh.2003.07.014.
Background: PubMed 26016707Wang XW, Cao JB, Lv BS, Mi WD, Wang ZQ, Zhang C, Wang HL, Xu Z. Effect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta-analysis. Clin Exp Pharmacol Physiol. 2015 Aug;42(8):828-36. doi: 10.1111/1440-1681.12431.
Background: PubMed 26991622Li Y, Wang B, Zhang LL, He SF, Hu XW, Wong GT, Zhang Y. Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique. Anesth Analg. 2016 Apr;122(4):1202-10. doi: 10.1213/ANE.0000000000001165.
Background: PubMed 26446479Kim DJ, Kim SH, So KY, Jung KT. Effects of dexmedetomidine on smooth emergence from anaesthesia in elderly patients undergoing orthopaedic surgery. BMC Anesthesiol. 2015 Oct 7;15:139. doi: 10.1186/s12871-015-0127-4.
Background: PubMed 26005187Le Bot A, Michelet D, Hilly J, Maesani M, Dilly MP, Brasher C, Mantz J, Dahmani S. Efficacy of intraoperative dexmedetomidine compared with placebo for surgery in adults: a meta-analysis of published studies. Minerva Anestesiol. 2015 Oct;81(10):1105-17. Epub 2015 May 25.
Individual participant dataSharing planned: Yes

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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.

Dong-Xin Wang, MD, PhD principal investigator

Peking University First Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing dexmedetomidine and normal saline in people with Brain Neoplasms, run by Peking University First Hospital at 1 site in China.

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 9 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: finished, as of the sponsor's last update on 29 Sep 2016. 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 China. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Intelligence Quotient (time frame: At 3 months after surgery). 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 NCT02810899, which also lists 11 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 29 Sep 2016.