High Risk MC4R GenotypePhase 4NCT01844700

1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain

A Phase 4 study testing Ziprasidone and aripiprazole, quetiapine, or risperidone in people with High Risk MC4R Genotype and Low Risk MC4R Genotype, run by Northwell Health at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 13 to 18 years
Conditions the study is for: High Risk MC4R Genotype, Low Risk MC4R Genotype, One Week or Less Antipsychotic Lifetime Exposure
What is being tested?: Ziprasidone and aripiprazole, quetiapine, or risperidone
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: Jul 2013to Apr 2014
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 13 to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

age 13-18 years
English-speaking
DSM diagnoses that have an FDA indication for SGA use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of early-onset schizophrenia spectrum disorders; bipolar I disorder mania (and BP-NOS); irritability associated with autism spectrum disorder, as well as severe mood dysregulation (SMD) according to Leibenluft et al. (2011) with an ABC-irritability score of >/=18 Sexually active girls must agree to use two effective forms of birth control or be abstinent
Participant has a primary caretaker who has known the child well for at least 6 months before study entry Primary caretaker is able to participate in study appointments
Ability of child to participate in all aspects of the protocol per investigator clinical judgment.

Who cannot join

Major neurological or medical illnesses that affect weight (e.g., unstable thyroid disease), require a prohibited systemic medication (e.g., diabetes mellitus [insulin], chronic renal failure [steroids); Fasting glucose > 125 mg/dL on 2 occasions during screening
Any medication (other than currently prescribed psychotropic medications) that would significantly alter weight
Antidepressants not allowed for at least 2 weeks in BP-I or BP-NOS patients
DSM-IV diagnosis of anorexia or bulimia nervosa
DSM-IV diagnosis of Substance Dependence disorder (other than tobacco dependence) within the past month
Initial urine toxicology screen and follow-up screen indicate ongoing use of illicit substance

Show all 12Show fewer

Hypersensitivity to ZIP or UC antipsychotics
Pregnant, breast feeding or unwilling to comply with contraceptive requirements
Screening or baseline QTc > 450 msec
IQ < 55
Significant risk for dangerousness to self or to others
Ongoing or previously undisclosed child abuse requiring new department of social service intervention.

Trial locations and contacts

1 site in 1 country.

United States1 site

Zucker Hillside Hospital, Psychiatry Research
Glen Oaks, New York, 11004

Other trials in United States

About this study

We will conduct a 12-week, randomized open label study, comparing usual care (UC) antipsychotic treatment (aripiprazole, quetiapine, risperidone) with ziprasidone (ZIP) in children and adolescents aged 13-18 years old. Patients will have 10 days or less lifetime antipsychotic exposure and be in clinical need for antipsychotic treatment for a pediatric psychiatric disorder with FDA indication for antipsychotic use, i.e., bipolar mania, schizophrenia-spectrum disorders, and irritability associated with autistic disorder. In addition, we will also include youth fulfilling research diagnostic criteria for severe mood dysregulation (SMD). Randomization will be stratified by high vs. low genetic risk for antipsychotic-induced weight gain based on MC4R genotype and the primary outcome will be weight change from baseline to endpoint between ZIP and UC antipsychotic treatment in each of the two genotype groups. As detailed below, other metabolic and cardiac safety parameters will also be measured and compared across treatments in each of the genotype groups.

Conditions: High Risk MC4R Genotype, Low Risk MC4R Genotype, One Week or Less Antipsychotic Lifetime Exposure
Being tested: Ziprasidone, aripiprazole, quetiapine, or risperidone
Keywords: MC4R genotype, antipsychotic induced weight gain, pediatric population

What participants receive

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

ZiprasidoneDrug
Also called Geodon
random assignment to ZIP (20-160mg/d, bid dosing)
aripiprazole, quetiapine, or risperidoneDrug
Also called Abilify, Seroquel, Risperdal
random assignement to Usual Care antipsychotic UC antipsychotic (aripiprazole 2-30mg/d, quetiapine 25-800mg/d or risperidone 0.1-8mg/d)

Study groups in NCT01844700
Study group	Role	What they receive
Ziprasidone	Active comparator	(20-160mg/d, bid) for 12 weeks Receives: Drug: Ziprasidone
Aripiprazole, quetiapine, risperidone	Active comparator	Aripiprazole (2-30mg/d), Quetiapine (25-800mg/d) or Risperidone (0.1-8mg/d) for 12 weeks Receives: Drug: aripiprazole, quetiapine, or risperidone

What is being measured

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

Weight Change
Measured: baseline to week 12

Secondary outcomes (3)

Percent Weight Change Compared to Baseline Weight
Measured: baseline to week 12
BMI Z-scores
Measured: baseline to week 12
BMI Percentile
Measured: baseline to week 12

Timeline

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

Jul 2013Apr 2014

First posted1 May 2013 (estimated)
Study startJul 2013
Primary completionApr 2014
Study completionApr 2014

Why it stopped: very slow recruitment, no sufficient results

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (87)Papers the sponsor has linked to this study.
Other trials for High Risk MC4R GenotypeStudies of the same condition, open and under way.
More trials run by Northwell HealthThe 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 4
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01844700
Sponsor's protocol ID: 12-403A
Status last verified: Jan 2016
First submitted: 29 Apr 2013
Last updated: 5 Feb 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.
PubMed 10553730
Axelson D, Birmaher B, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Bridge J, Keller M. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Oct;63(10):1139-48. doi: 10.1001/archpsyc.63.10.1139.
PubMed 17015816
Basile VS, Masellis M, McIntyre RS, Meltzer HY, Lieberman JA, Kennedy JL. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psychiatry. 2001;62 Suppl 23:45-66.
PubMed 11603885
Beckers S, Zegers D, de Freitas F, Mertens IL, Van Gaal LF, Van Hul W. Association study of MC4R with complex obesity and replication of the rs17782313 association signal. Mol Genet Metab. 2011 May;103(1):71-5. doi: 10.1016/j.ymgme.2011.01.007. Epub 2011 Jan 22.
PubMed 21303735
Birmaher B, Axelson D, Goldstein B, Strober M, Gill MK, Hunt J, Houck P, Ha W, Iyengar S, Kim E, Yen S, Hower H, Esposito-Smythers C, Goldstein T, Ryan N, Keller M. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009 Jul;166(7):795-804. doi: 10.1176/appi.ajp.2009.08101569. Epub 2009 May 15.
PubMed 19448190
Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Keller M. Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Feb;63(2):175-83. doi: 10.1001/archpsyc.63.2.175.
PubMed 16461861
Branson R, Potoczna N, Kral JG, Lentes KU, Hoehe MR, Horber FF. Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N Engl J Med. 2003 Mar 20;348(12):1096-103. doi: 10.1056/NEJMoa021971.
PubMed 12646666
Brotons C, Ribera A, Perich RM, Abrodos D, Magana P, Pablo S, Terradas D, Fernandez F, Permanyer G. Worldwide distribution of blood lipids and lipoproteins in childhood and adolescence: a review study. Atherosclerosis. 1998 Jul;139(1):1-9. doi: 10.1016/s0021-9150(98)00056-2.
PubMed 9699886
Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, Balding D, Scott J, Kooner JS. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet. 2008 Jun;40(6):716-8. doi: 10.1038/ng.156. Epub 2008 May 4.
PubMed 18454146
Chen AS, Metzger JM, Trumbauer ME, Guan XM, Yu H, Frazier EG, Marsh DJ, Forrest MJ, Gopal-Truter S, Fisher J, Camacho RE, Strack AM, Mellin TN, MacIntyre DE, Chen HY, Van der Ploeg LH. Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res. 2000 Apr;9(2):145-54. doi: 10.1023/a:1008983615045.
PubMed 10951699
Comer JS, Mojtabai R, Olfson M. National trends in the antipsychotic treatment of psychiatric outpatients with anxiety disorders. Am J Psychiatry. 2011 Oct;168(10):1057-65. doi: 10.1176/appi.ajp.2011.11010087. Epub 2011 Jul 28.
PubMed 21799067
Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med. 2003 Aug;157(8):821-7. doi: 10.1001/archpedi.157.8.821.
PubMed 12912790
Correll CU, Kratochvil CJ, March JS. Developments in pediatric psychopharmacology: focus on stimulants, antidepressants, and antipsychotics. J Clin Psychiatry. 2011 May;72(5):655-70. doi: 10.4088/JCP.11r07064.
PubMed 21658348
Correll CU, Lencz T, Malhotra AK. Antipsychotic drugs and obesity. Trends Mol Med. 2011 Feb;17(2):97-107. doi: 10.1016/j.molmed.2010.10.010. Epub 2010 Dec 22.
PubMed 21185230
Correll CU, Malhotra AK. Pharmacogenetics of antipsychotic-induced weight gain. Psychopharmacology (Berl). 2004 Aug;174(4):477-89. doi: 10.1007/s00213-004-1949-9. Epub 2004 Jul 8.
PubMed 15243737

Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain
ClinicalTrials.gov ID: NCT01844700
Acronym / sponsor ID: 12-403A
Conditions: High Risk MC4R Genotype, Low Risk MC4R Genotype, One Week or Less Antipsychotic Lifetime Exposure
Keywords: MC4R genotype, antipsychotic induced weight gain, pediatric population
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: very slow recruitment, no sufficient results
Enrolment: 14 participants (actual)
Lead sponsor: Northwell HealthUniversity, hospital or other
Study start: Jul 2013
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 1 May 2013 (estimated)
Results: Posted 5 Feb 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Ziprasidone	Active comparator	Drug: Ziprasidone(20-160mg/d, bid) for 12 weeks
Aripiprazole, quetiapine, risperidone	Active comparator	Drug: aripiprazole, quetiapine, or risperidoneAripiprazole (2-30mg/d), Quetiapine (25-800mg/d) or Risperidone (0.1-8mg/d) for 12 weeks

Who may qualify

Ages: 13 to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (5 listed)

age 13-18 years
English-speaking
DSM diagnoses that have an FDA indication for SGA use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of early-onset schizophrenia spectrum disorders; bipolar I disorder mania (and BP-NOS); irritability associated with autism spectrum disorder, as well as severe mood dysregulation (SMD) according to Leibenluft et al. (2011) with an ABC-irritability score of >/=18 Sexually active girls must agree to use two effective forms of birth control or be abstinent
Participant has a primary caretaker who has known the child well for at least 6 months before study entry Primary caretaker is able to participate in study appointments
Ability of child to participate in all aspects of the protocol per investigator clinical judgment.

Key exclusion criteria (12 listed)

Major neurological or medical illnesses that affect weight (e.g., unstable thyroid disease), require a prohibited systemic medication (e.g., diabetes mellitus [insulin], chronic renal failure [steroids); Fasting glucose > 125 mg/dL on 2 occasions during screening
Any medication (other than currently prescribed psychotropic medications) that would significantly alter weight
Antidepressants not allowed for at least 2 weeks in BP-I or BP-NOS patients
DSM-IV diagnosis of anorexia or bulimia nervosa
DSM-IV diagnosis of Substance Dependence disorder (other than tobacco dependence) within the past month

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
ZiprasidoneAlso: Geodonrandom assignment to ZIP (20-160mg/d, bid dosing)	Drug	Ziprasidone
aripiprazole, quetiapine, or risperidoneAlso: Abilify, Seroquel, Risperdalrandom assignement to Usual Care antipsychotic UC antipsychotic (aripiprazole 2-30mg/d, quetiapine 25-800mg/d or risperidone 0.1-8mg/d)	Drug	Aripiprazole, quetiapine, risperidone

Primary outcome

Weight Change
Time frame: baseline to week 12

3 secondary outcomes

Percent Weight Change Compared to Baseline Weight
Time frame: baseline to week 12
BMI Z-scores
Time frame: baseline to week 12
BMI Percentile
Time frame: baseline to week 12

Results and safety

Results posted to the registry on 5 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ziprasidone	4	1
Aripiprazole, Quetiapine, Risperidone	3	2

Primary outcome: Weight Change

Time frame: baseline to week 12. Mean (Standard Deviation). Unit: lbs

Measure	Ziprasidone n = 4	Aripiprazole, Quetiapine, Risperidone n = 3
baseline	120.5 (8.23)	118.5 (27.92)
week 12 (n=1,2)	151 (0)	141 (7.06)

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ziprasidone	0 of 4 (0%)	0 of 4 (0%)	Not reported
Aripiprazole, Quetiapine, Risperidone	0 of 3 (0%)	0 of 3 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 10553730Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.
Background: PubMed 17015816Axelson D, Birmaher B, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Bridge J, Keller M. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Oct;63(10):1139-48. doi: 10.1001/archpsyc.63.10.1139.
Background: PubMed 11603885Basile VS, Masellis M, McIntyre RS, Meltzer HY, Lieberman JA, Kennedy JL. Genetic dissection of atypical antipsychotic-induced weight gain: novel preliminary data on the pharmacogenetic puzzle. J Clin Psychiatry. 2001;62 Suppl 23:45-66.
Background: PubMed 21303735Beckers S, Zegers D, de Freitas F, Mertens IL, Van Gaal LF, Van Hul W. Association study of MC4R with complex obesity and replication of the rs17782313 association signal. Mol Genet Metab. 2011 May;103(1):71-5. doi: 10.1016/j.ymgme.2011.01.007. Epub 2011 Jan 22.
Background: PubMed 19448190Birmaher B, Axelson D, Goldstein B, Strober M, Gill MK, Hunt J, Houck P, Ha W, Iyengar S, Kim E, Yen S, Hower H, Esposito-Smythers C, Goldstein T, Ryan N, Keller M. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. Am J Psychiatry. 2009 Jul;166(7):795-804. doi: 10.1176/appi.ajp.2009.08101569. Epub 2009 May 15.
Background: PubMed 16461861Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Keller M. Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Feb;63(2):175-83. doi: 10.1001/archpsyc.63.2.175.
Background: PubMed 12646666Branson R, Potoczna N, Kral JG, Lentes KU, Hoehe MR, Horber FF. Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N Engl J Med. 2003 Mar 20;348(12):1096-103. doi: 10.1056/NEJMoa021971.
Background: PubMed 9699886Brotons C, Ribera A, Perich RM, Abrodos D, Magana P, Pablo S, Terradas D, Fernandez F, Permanyer G. Worldwide distribution of blood lipids and lipoproteins in childhood and adolescence: a review study. Atherosclerosis. 1998 Jul;139(1):1-9. doi: 10.1016/s0021-9150(98)00056-2.
Background: PubMed 18454146Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, Balding D, Scott J, Kooner JS. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet. 2008 Jun;40(6):716-8. doi: 10.1038/ng.156. Epub 2008 May 4.
Background: PubMed 10951699Chen AS, Metzger JM, Trumbauer ME, Guan XM, Yu H, Frazier EG, Marsh DJ, Forrest MJ, Gopal-Truter S, Fisher J, Camacho RE, Strack AM, Mellin TN, MacIntyre DE, Chen HY, Van der Ploeg LH. Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res. 2000 Apr;9(2):145-54. doi: 10.1023/a:1008983615045.
Background: PubMed 21799067Comer JS, Mojtabai R, Olfson M. National trends in the antipsychotic treatment of psychiatric outpatients with anxiety disorders. Am J Psychiatry. 2011 Oct;168(10):1057-65. doi: 10.1176/appi.ajp.2011.11010087. Epub 2011 Jul 28.
Background: PubMed 12912790Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med. 2003 Aug;157(8):821-7. doi: 10.1001/archpedi.157.8.821.

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.

The record lists no contact. Use the official record to reach the sponsor.

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 Ziprasidone and aripiprazole, quetiapine, or risperidone in people with High Risk MC4R Genotype and Low Risk MC4R Genotype, run by Northwell Health at 1 site in United States.

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 5 inclusion and 12 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 5 Feb 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 United States. 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. 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?

Yes. Results are posted in the registry (first posted 5 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Weight Change (time frame: baseline to week 12). 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 NCT01844700, which also lists 87 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 5 Feb 2016.