SchizophreniaPhase 4NCT00345033

Effectiveness of Aripiprazole for Improving Side Effects of Clozapine in the Treatment of People With Schizophrenia

A Phase 4 study testing Aripiprazole in people with Schizophrenia and Insulin Resistance, run by Massachusetts General Hospital at 1 site in United States.

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

This study will evaluate the effects of combination treatment with aripiprazole and clozapine on insulin resistance, blood fat levels, and weight gain in people diagnosed with schizophrenia. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Schizophrenia, Insulin Resistance
What is being tested?: Aripiprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: 1 siteUnited States
Study dates: Mar 2005to Oct 2010
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of schizophrenia (any subtype) or schizoaffective disorder (any subtype)
Treatment with clozapine for at least 1 year
Stable dose of clozapine for at least 1 month
Well established compliance with outpatient medications
Female participants of non-childbearing potential or of childbearing potential and willing to practice appropriate birth control methods (complete abstinence from sexual intercourse, female sterilization, sterilization of male partner, implants of levonorgestrel, injectable progestogen, oral contraceptives, intrauterine devices, or double barrier methods of contraception using spermicide with either a condom or diaphragm) during the study

Who cannot join

Current substance abuse
Psychiatrically unstable
Significant medical illness, including severe cardiovascular, hepatic, or renal disease
History of immunosuppression
Current or recent radiation or chemotherapy treatment for cancer
Chronic use of steroids
Pregnant or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital Schizophrenia Program
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Aripiprazole for Clozapine Associated Medical Morbidity

This study will evaluate the effects of combination treatment with aripiprazole and clozapine on insulin resistance, blood fat levels, and weight gain in people diagnosed with schizophrenia.

Read the detailed description

Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations and delusions, as well as overall difficulty with everyday functioning. Although the medications available to treat the disorder are generally effective, many cause undesirable side effects. Clozapine, for example, is a strong tranquilizer that functions like an antipsychotic medication. It has been shown to be effective in reducing the symptoms of schizophrenia, but can bring about serious side effects, including heart failure, weight gain, and diabetes. Aripiprazole, an atypical antipsychotic medication, has been shown to have fewer side effects than older antipsychotic drugs. The addition of aripiprazole to a clozapine treatment regimen may reduce the negative side effects of clozapine. This study will evaluate the effects of combination treatment with aripiprazole and clozapine on insulin resistance, blood fat levels, and weight gain in people with schizophrenia.

Individuals interested in participating in this 8-week, double-blind study will first attend a screening session at the study site. Medical and psychiatric evaluations will be completed, blood samples will be taken, and an EKG will be performed. Eligible participants will undergo baseline assessments and then be randomly assigned to receive either aripiprazole or placebo in addition to their prescribed dose of clozapine. Participants will take one 15-mg capsule of their assigned medication once a day for 8 weeks. Study visits will occur biweekly for the first 8 weeks, followed by one final follow-up visit at Week 12. At each study visit, medication will be distributed, and the following criteria will be assessed: vital signs; weight; complete blood count; medication side effects; and extrapyramidal symptoms (EPS), which are potential neurological side effects of antipsychotic medications and may include involuntary movements, tremors, and rigidity. The Week 8 visit will include an EKG, and assessments of the following criteria: vital signs; medication side effects; treatment efficacy; blood counts; weight and height; and waist and hip circumference. At baseline and Week 8, participants will also undergo a frequently sampled intravenous glucose tolerance test (FSIVGTT). This involves intravenous infusion of glucose followed by frequent blood sampling to measure insulin and glucose concentrations. During the 4 days prior to each FSIVGTT, participants will record their food intake and wear an activity monitor.

Conditions: Schizophrenia, Insulin Resistance
Being tested: Aripiprazole, Placebo
Keywords: Glucose Metabolism
Medical subject headings: Schizophrenia, Insulin Resistance

What participants receive

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

AripiprazoleDrug
15-mg dose once a day for 8 weeks
PlaceboDrug
1 tablet placebo dose once a day for 8 weeks

Study groups in NCT00345033
Study group	Role	What they receive
1	Experimental	Participants will take aripiprazole 15mg/day for 8 weeks. Receives: Drug: Aripiprazole
2	Placebo comparator	Participants will take placebo for 8 weeks. Receives: Drug: Placebo

What is being measured

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

Change in Total Cholesterol
A comparison of aripiprazole group and placebo group in change in total cholesterol measured at Baseline and Week 8.
Measured: Measured at Baseline and Week 8
Change in Weight
A comparison between aripiprazole group and placebo group in change in weight measured at Baseline and Week 8.
Measured: Measured at Baseline and Week 8
Change in Body Mass Index (BMI)
A comparison between aripiprazole group and placebo group of change in Body Mass Index (BMI) measured at Baseline and Week 8.
Measured: Measured at Baseline and Week 8
Change in Glucose Metabolism
A comparison between the aripiprazole group and placebo group in change in glucose metabolism measured at Baseline and Week 8.
Measured: Measured at Baseline and Week 8
Change in Triglycerides
Measured: Measured at Baseline and Week 8
Change in Insulin Resistance
A comparison between aripiprazole group and placebo group of change in insulin resistance measured at Baseline and Week 8.
Measured: Measured at Baseline and Week 8

Timeline

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

Mar 2005Oct 2010

First posted27 Jun 2006 (estimated)
Study startMar 2005
Primary completionOct 2009
Study completionOct 2010

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 (7)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe 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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00345033
Sponsor's protocol ID: R01MH072635
Other IDs: R01MH072635, DSIR 83-ATAP
Status last verified: Jun 2014
First submitted: 23 Jun 2006
Last updated: 23 Jun 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Casey DE, Carson WH, Saha AR, Liebeskind A, Ali MW, Jody D, Ingenito GG; Aripiprazole Study Group. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berl). 2003 Apr;166(4):391-9. doi: 10.1007/s00213-002-1344-3. Epub 2003 Feb 28.
PubMed 12610718
Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999 Sep-Oct;40(5):438-43. doi: 10.1016/S0033-3182(99)71210-7. No abstract available.
PubMed 10479950
Hadigan C, Miller K, Corcoran C, Anderson E, Basgoz N, Grinspoon S. Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 1999 Jun;84(6):1932-7. doi: 10.1210/jcem.84.6.5738.
PubMed 10372689
Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.
PubMed 10831479
Marder SR, McQuade RD, Stock E, Kaplita S, Marcus R, Safferman AZ, Saha A, Ali M, Iwamoto T. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res. 2003 Jun 1;61(2-3):123-36. doi: 10.1016/s0920-9964(03)00050-1.
PubMed 12729864
Visser M, Fuerst T, Lang T, Salamone L, Harris TB. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health, Aging, and Body Composition Study--Dual-Energy X-ray Absorptiometry and Body Composition Working Group. J Appl Physiol (1985). 1999 Oct;87(4):1513-20. doi: 10.1152/jappl.1999.87.4.1513.
PubMed 10517786
Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002 Oct;63(10):856-65. doi: 10.4088/jcp.v63n1002.
PubMed 12416594

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?

See locations

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Aripiprazole for Clozapine Associated Medical Morbidity
ClinicalTrials.gov ID: NCT00345033
Acronym / sponsor ID: R01MH072635
Conditions: Schizophrenia, Insulin Resistance
Keywords: Glucose Metabolism
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: Mar 2005
Primary completion: Oct 2009 (actual)
Study completion: Oct 2010 (actual)
First posted: 27 Jun 2006 (estimated)
Results: Posted 13 Sep 2012

Clinical summary

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

This study will evaluate the effects of combination treatment with aripiprazole and clozapine on insulin resistance, blood fat levels, and weight gain in people diagnosed with schizophrenia.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: AripiprazoleParticipants will take aripiprazole 15mg/day for 8 weeks.
2	Placebo comparator	Drug: PlaceboParticipants will take placebo for 8 weeks.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Diagnosis of schizophrenia (any subtype) or schizoaffective disorder (any subtype)
Treatment with clozapine for at least 1 year
Stable dose of clozapine for at least 1 month
Well established compliance with outpatient medications
Female participants of non-childbearing potential or of childbearing potential and willing to practice appropriate birth control methods (complete abstinence from sexual intercourse, female sterilization, sterilization of male partner, implants of levonorgestrel, injectable progestogen, oral contraceptives, intrauterine devices, or double barrier methods of contraception using spermicide with either a condom or diaphragm) during the study

Key exclusion criteria (7 listed)

Current substance abuse
Psychiatrically unstable
Significant medical illness, including severe cardiovascular, hepatic, or renal disease
History of immunosuppression
Current or recent radiation or chemotherapy treatment for cancer

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
Aripiprazole15-mg dose once a day for 8 weeks	Drug	1
Placebo1 tablet placebo dose once a day for 8 weeks	Drug	2

Primary outcome

Change in Total Cholesterol
Time frame: Measured at Baseline and Week 8
A comparison of aripiprazole group and placebo group in change in total cholesterol measured at Baseline and Week 8.
Change in Weight
Time frame: Measured at Baseline and Week 8
A comparison between aripiprazole group and placebo group in change in weight measured at Baseline and Week 8.
Change in Body Mass Index (BMI)
Time frame: Measured at Baseline and Week 8
A comparison between aripiprazole group and placebo group of change in Body Mass Index (BMI) measured at Baseline and Week 8.
Change in Glucose Metabolism
Time frame: Measured at Baseline and Week 8
A comparison between the aripiprazole group and placebo group in change in glucose metabolism measured at Baseline and Week 8.
Change in Triglycerides
Time frame: Measured at Baseline and Week 8
Change in Insulin Resistance
Time frame: Measured at Baseline and Week 8
A comparison between aripiprazole group and placebo group of change in insulin resistance measured at Baseline and Week 8.

Results and safety

Results posted to the registry on 13 Sep 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aripiprazole	20	16
Placebo	18	14

Primary outcome: Change in Total Cholesterol

Time frame: Measured at Baseline and Week 8. Mean (Standard Deviation). Unit: mg/dL

Measure	Aripiprazole n = 16	Placebo n = 14
Value	-15.3 (33.3)	5.6 (34.0)

Aripiprazole vs Placebo: p = 0.125, ANCOVA

Population analysed: The number of participants for analysis (intent to treat) were those that completed the study (N = 30).

Primary outcome: Change in Weight

Time frame: Measured at Baseline and Week 8. Mean (Standard Deviation). Unit: kg

Measure	Aripiprazole n = 16	Placebo n = 14
Value	-1.5 (2.3)	0.3 (2.3)

Aripiprazole vs Placebo: p = 0.109, ANCOVA

Population analysed: The number of participants for analysis (intent to treat) were those that completed the study (N=30).

Primary outcome: Change in Body Mass Index (BMI)

Time frame: Measured at Baseline and Week 8. Mean (Standard Deviation). Unit: kg/m^2

Measure	Aripiprazole n = 16	Placebo n = 14
Value	-0.52 (0.79)	0.03 (0.85)

Aripiprazole vs Placebo: p = 0.229, ANCOVA

Population analysed: The number of participants for analysis (intent to treat) were those that completed the study (N=30).

Primary outcome: Change in Glucose Metabolism

Time frame: Measured at Baseline and Week 8. Mean (Standard Deviation). Unit: min^-1

Measure	Aripiprazole n = 16	Placebo n = 14
Value	0.003 (0.006)	-0.005 (0.007)

Aripiprazole vs Placebo: p = 0.010, ANCOVA

Population analysed: The number of participants for analysis (intent to treat) were those that completed the study (N=30).

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aripiprazole	0 of 16 (0%)	4 of 16 (25%)	Not reported
Placebo	0 of 14 (0%)	3 of 14 (21.4%)	Not reported

Limitations and caveats (from the sponsor): The limitations of this study include the relatively small sample size, short intervention period (8 weeks) and the lack of generalizability of our findings to patients with schizophrenia treated by antipsychotic agents other than clozapine.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12610718Casey DE, Carson WH, Saha AR, Liebeskind A, Ali MW, Jody D, Ingenito GG; Aripiprazole Study Group. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berl). 2003 Apr;166(4):391-9. doi: 10.1007/s00213-002-1344-3. Epub 2003 Feb 28.
Background: PubMed 10479950Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999 Sep-Oct;40(5):438-43. doi: 10.1016/S0033-3182(99)71210-7. No abstract available.
Background: PubMed 10372689Hadigan C, Miller K, Corcoran C, Anderson E, Basgoz N, Grinspoon S. Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 1999 Jun;84(6):1932-7. doi: 10.1210/jcem.84.6.5738.
Background: PubMed 10831479Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81. doi: 10.1176/appi.ajp.157.6.975.
Background: PubMed 12729864Marder SR, McQuade RD, Stock E, Kaplita S, Marcus R, Safferman AZ, Saha A, Ali M, Iwamoto T. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res. 2003 Jun 1;61(2-3):123-36. doi: 10.1016/s0920-9964(03)00050-1.
Background: PubMed 10517786Visser M, Fuerst T, Lang T, Salamone L, Harris TB. Validity of fan-beam dual-energy X-ray absorptiometry for measuring fat-free mass and leg muscle mass. Health, Aging, and Body Composition Study--Dual-Energy X-ray Absorptiometry and Body Composition Working Group. J Appl Physiol (1985). 1999 Oct;87(4):1513-20. doi: 10.1152/jappl.1999.87.4.1513.
Background: PubMed 12416594Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002 Oct;63(10):856-65. doi: 10.4088/jcp.v63n1002.

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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.

David C. Henderson, MD principal investigator

Massachusetts General 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 Aripiprazole in people with Schizophrenia and Insulin Resistance, run by Massachusetts General Hospital 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 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: finished, as of the sponsor's last update on 23 Jun 2014. 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 13 Sep 2012). 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 Total Cholesterol (time frame: Measured at Baseline and Week 8). The study lists 6 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 NCT00345033, which also lists 7 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 23 Jun 2014.