HealthyPhase 4NCT01920802
Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking Iloperidone or Olanzapine or Placebo
A Phase 4 study testing olanzapine and iloperidone in people with Healthy, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
The purpose of this pilot randomized clinical trial is to begin to delineate the pathophysiological changes associated with antipsychotic associated metabolic side effects. The study will be performed in 36 healthy people between the ages of 18 and 30, who have never taken an antipsychotic, will undergo baseline… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- olanzapine and iloperidone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Sep 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 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female between the ages of 18-35 with no history of any Axis-I diagnosis
- Does not meet criteria for substance abuse or dependence in the past six months
- Female subjects will use barrier-method, non-hormonal contraception
- Capacity to understand all the relevant risks and potential benefits of the study (informed consent)
- Must be able to speak and read English
Who cannot join
- Current or past Axis I psychiatric diagnosis, including alcohol or substance abuse or dependence (except nicotine or caffeine), but not including minor Axis I disorders (e.g. simple phobia)
- Lifetime use of psychotropic medications, including antipsychotics, antidepressants, mood stabilizers, and anxiolytics
- Presence or history of medical or neurological illness that, in the judgment of the investigator, could influence the results of the study
- Diagnosis of diabetes, hemoglobin A1C > 6.5, hypertension, or dyslipidemias, or elevated random or fasting glucose, abnormal lipid levels, BP 130/85
- BMI 25 or < 19, history of BMI >35, and/or waist circumference >35 inches for females, 40 inches for males
- Subjects who are pregnant or breast-feeding or planning to become pregnant during the study
Show all 19Show fewer
- Acute suicidality
- Meets criteria for a Diagnostic and Statistical Manual, Version 4 (DSM-IV) defined eating disorder
- Use of, or clinical indication for, one or more of the following medications: lithium, anti-epileptic medication, steroids (oral or inhaled), stimulants, serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants, thyroid supplementation, sibutramine, metformin, thiazolidinediones, beta-blockers, clonidine, niacin
- Subjects who have had >10% change in their body weight within the three months prior to enrollment
- HIV positive subjects
- Presence of mental retardation or pervasive developmental disorder
- History of recent (within 6 months) significant self-injurious behavior or violence
- Daily multivitamin or B-complex vitamin use
- A known history of dieting and difficulty with weight loss
- A strong family history of diabetes and/or heart disease
- History of congenital long QT syndrome or prolonged corrected QT interval (QTc) on screening EKG (>450ms)
- Concomitant use of any medication that inhibits 2D6 or 3A4 metabolism
- Low serum potassium or magnesium
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Quantitative Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking the Antipsychotic Medications Fanapt (Iloperidone) or Zyprexa (Olanzapine) or Placebo
The purpose of this pilot randomized clinical trial is to begin to delineate the pathophysiological changes associated with antipsychotic associated metabolic side effects. The study will be performed in 36 healthy people between the ages of 18 and 30, who have never taken an antipsychotic, will undergo baseline laboratory tests before being randomized to 5mg BID of olanzapine or 6mg BID of iloperidone or placebo to take for up to 4 weeks. The primary outcome measure will be a correlation of early changes in leptin with weight gain. We will also record changes in food intake, resting metabolic rate, oral glucose tolerance and fasting insulin and glucose levels, lipids and inflammation markers. Subjects will be followed closely to monitor for safety throughout the 4-week study and will be discontinued if there is a medically significant change in metabolic status or other antipsychotic side effects. Metabolic assessments will be performed again at the time of discontinuation or at the end of an 4-week period, and change from baseline in the two treatment groups will be compared.
Read the detailed description
Study hypotheses:
- Early changes (baseline vs day 3) in leptin will correlate with later changes in weight (at study termination.)
- Olanzapine will cause the greatest increase in calorie consumption from baseline on the multi-item meal compared with iloperidone or placebo.
- Olanzapine subjects will report the greatest frequency/quantity of eating in food diaries, and report increased preference for calorically dense foods (ie, higher fat content) compared to iloperidone or placebo.
- Early markers of endocrine changes caused by olanzapine will be greater than those caused by iloperidone or placebo, and these early changes will correlate with weight gain.
- Olanzapine will have greater effects on glucose homeostasis than iloperidone or placebo, and these effects will be separate from effects on body weight and composition.
- Early signs of metabolic disturbance, including glucose intolerance (greater excursion on OGTT) and insulin resistance (higher plasma insulin) will precede any significant weight gain.
- Early evidence of glucose intolerance and/or insulin resistance will predict greater metabolic derangements with further dosing of olanzapine, as evidenced by exacerbated glucose intolerance on OGTT or higher plasma glucose/insulin levels. These effects may not necessarily parallel weight gain.
- Olanzapine will be associated with greater markers of inflammation than iloperidone or placebo.
- Conditions
- Healthy
- Being tested
- olanzapine, iloperidone, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olanzapineDrug
Also called Zyprexa
5mg BID up to 4 weeks
iloperidoneDrug
Also called Fanapt
6 mg BID up to 4 weeks
PlaceboDrug
BID up to 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| olanzapine | Experimental | 5mg BID olanzapine for up to 4 weeks Receives: Drug: olanzapine |
| iloperidone | Experimental | 6mg BID iloperidone up to 4 weeks Receives: Drug: iloperidone |
| placebo | Placebo comparator | BID placebo up to 4 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Body Weight
Delineate a pathophysiological mechanism of antipsychotic induced weight gain
Measured: baseline and 6 week visit
Change in Adiposity
Total fat mass (excluding head) from baseline to Day 28
Measured: Baseline to Day 28
Secondary outcomes (1)
Change in Leptin
Leptin levels measured at Day 3 compared to baseline
Measured: change in baseline to Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2013 (estimated)
- Study startNov 2012
- Primary completionAug 2014
- Study completionSep 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Jeffrey Lieberman, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01920802
- Sponsor's protocol ID
- 6525
- Status last verified
- Jan 2017
- First submitted
- 8 Aug 2013
- Last updated
- 20 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ballon JS, Pajvani UB, Mayer LE, Freyberg Z, Freyberg R, Contreras I, Rosenbaum M, Leibel RL, Lieberman JA. Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo. J Psychopharmacol. 2018 May;32(5):533-540. doi: 10.1177/0269881118754708. Epub 2018 Feb 15.
PubMed 29444618
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking the Antipsychotic Medications Fanapt (Iloperidone) or Zyprexa (Olanzapine) or Placebo
- ClinicalTrials.gov ID
- NCT01920802
- Acronym / sponsor ID
- 6525
- Conditions
- Healthy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Nov 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 12 Aug 2013 (estimated)
- Results
- Posted 20 Mar 2017
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 pilot randomized clinical trial is to begin to delineate the pathophysiological changes associated with antipsychotic associated metabolic side effects. The study will be performed in 36 healthy people between the ages of 18 and 30, who have never taken an antipsychotic, will undergo baseline laboratory tests before being randomized to 5mg BID of olanzapine or 6mg BID of iloperidone or placebo to take for up to 4 weeks. The primary outcome measure will be a correlation of early changes in leptin with weight gain. We will also record changes in food intake, resting metabolic rate, oral glucose tolerance and fasting insulin and glucose levels, lipids and inflammation markers. Subjects will be followed closely to monitor for safety throughout the 4-week study and will be discontinued if there is a medically significant change in metabolic status or other antipsychotic side effects. Metabolic assessments will be performed again at the time of discontinuation or at the end of an 4-week period, and change from baseline in the two treatment groups will be compared.
Detailed description
Study hypotheses:
- Early changes (baseline vs day 3) in leptin will correlate with later changes in weight (at study termination.)
- Olanzapine will cause the greatest increase in calorie consumption from baseline on the multi-item meal compared with iloperidone or placebo.
- Olanzapine subjects will report the greatest frequency/quantity of eating in food diaries, and report increased preference for calorically dense foods (ie, higher fat content) compared to iloperidone or placebo.
- Early markers of endocrine changes caused by olanzapine will be greater than those caused by iloperidone or placebo, and these early changes will correlate with weight gain.
- Olanzapine will have greater effects on glucose homeostasis than iloperidone or placebo, and these effects will be separate from effects on body weight and composition.
- Early signs of metabolic disturbance, including glucose intolerance (greater excursion on OGTT) and insulin resistance (higher plasma insulin) will precede any significant weight gain.
- Early evidence of glucose intolerance and/or insulin resistance will predict greater metabolic derangements with further dosing of olanzapine, as evidenced by exacerbated glucose intolerance on OGTT or higher plasma glucose/insulin levels. These effects may not necessarily parallel weight gain.
- Olanzapine will be associated with greater markers of inflammation than iloperidone or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| olanzapine | Experimental | Drug: olanzapine5mg BID olanzapine for up to 4 weeks |
| iloperidone | Experimental | Drug: iloperidone6mg BID iloperidone up to 4 weeks |
| placebo | Placebo comparator | Drug: PlaceboBID placebo up to 4 weeks |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Male or female between the ages of 18-35 with no history of any Axis-I diagnosis
- Does not meet criteria for substance abuse or dependence in the past six months
- Female subjects will use barrier-method, non-hormonal contraception
- Capacity to understand all the relevant risks and potential benefits of the study (informed consent)
- Must be able to speak and read English
Key exclusion criteria (19 listed)
- Current or past Axis I psychiatric diagnosis, including alcohol or substance abuse or dependence (except nicotine or caffeine), but not including minor Axis I disorders (e.g. simple phobia)
- Lifetime use of psychotropic medications, including antipsychotics, antidepressants, mood stabilizers, and anxiolytics
- Presence or history of medical or neurological illness that, in the judgment of the investigator, could influence the results of the study
- Diagnosis of diabetes, hemoglobin A1C > 6.5, hypertension, or dyslipidemias, or elevated random or fasting glucose, abnormal lipid levels, BP 130/85
- BMI 25 or < 19, history of BMI >35, and/or waist circumference >35 inches for females, 40 inches for males
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 |
|---|---|---|
| olanzapineAlso: Zyprexa5mg BID up to 4 weeks | Drug | olanzapine |
| iloperidoneAlso: Fanapt6 mg BID up to 4 weeks | Drug | iloperidone |
| PlaceboBID up to 4 weeks | Drug | placebo |
Primary outcome
Change in Body Weight
Time frame: baseline and 6 week visit
Delineate a pathophysiological mechanism of antipsychotic induced weight gain
Change in Adiposity
Time frame: Baseline to Day 28
Total fat mass (excluding head) from baseline to Day 28
1 secondary outcome
Change in Leptin
Time frame: change in baseline to Day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29444618Ballon JS, Pajvani UB, Mayer LE, Freyberg Z, Freyberg R, Contreras I, Rosenbaum M, Leibel RL, Lieberman JA. Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo. J Psychopharmacol. 2018 May;32(5):533-540. doi: 10.1177/0269881118754708. Epub 2018 Feb 15.
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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.
Jeffrey Lieberman, MD principal investigator
New York State Psychiatric Institute
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 olanzapine and iloperidone in people with Healthy, run by New York State Psychiatric Institute 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 19 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 20 Mar 2017. 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. 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?
Yes. Results are posted in the registry (first posted 20 Mar 2017). 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?
Change in Body Weight (time frame: baseline and 6 week visit). The study lists 2 primary outcomes in all. 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 NCT01920802, which also lists 1 linked publication.
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 20 Mar 2017.