Double-Blind Placebo Controlled Study of Adjunctive Aripiprazole for Symptomatic Hyperprolactinemia In Premenopausal Women With Schizophrenia (DAAMSEL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Maryland
Sponsor:
Information provided by (Responsible Party):
MPRC, University of Maryland
ClinicalTrials.gov Identifier:
NCT01338298
First received: April 17, 2011
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

Prolactin is a hormone that naturally occurs in the body. Some women taking antipsychotic medications may have high levels of prolactin in their bodies. High levels of prolactin may cause women to have problems with sex or satisfaction from sex. It may also cause women to have fewer or no menstrual periods. It may also cause the production of breast milk and may contribute to long term bone loss.

In this study, the investigators are testing whether taking adding a low dose of an antipsychotic medication called aripiprazole may help improve high prolactin levels and help with sexual dysfunction or problems with menstrual periods. The investigators are also looking to see if it may slow the loss of bones. This medication has been shown to be helpful for improving symptoms of schizophrenia.


Condition Intervention
Hyperprolactinemia
Drug: Aripiprazole
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind Placebo Controlled Study of Adjunctive Aripiprazole for Symptomatic Hyperprolactinemia In Premenopausal Women With Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • To determine if adjunct aripiprazole will resolve or improve prolactin related hormonal side effects (amenorrhea, oligomenorrhea, galactorrhea). [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    We will assess this outcome by monitoring the return of menstruation and the elimination of lactation. We hypothesize that adjunct aripiprazole will resolve hormonal effects in women with symptomatic hyperprolactinemia stabilized on risperidone (or paliperidone).


Secondary Outcome Measures:
  • To test whether adjunctive aripiprazole will improve quality/perceived quality of life. [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    We will measure if patients' symptoms improve, improvement in their sexual dysfunction or distress and if they feel better with the elimination of the side effects. We hypothesize that aripiprazole will improve psychiatric symptoms, quality of life, sexual functioning and perceived wellness relative to placebo in women stabilized on risperidone (or paliperidone).

  • To identify if adjunct aripiprazole will improve bone turnover as measured by assays of osteoblastic and osteoclastic activity. [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    We will measure blood and urine tests to determine if the adjunct treatment will preserve and prevent bone loss. We hypothesize that osteoclastic activity will be greater and osteoclastic activity will be less in women treated with adjunct aripiprazole relative to placebo in women stabilized on risperidone (or paliperidone).

  • To examine side effects associated with adjunctive aripiprazole versus placebo and conduct a cost analysis of adjunctive aripiprazole use. [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    We will measure if the benefits from the adjunctive treatment outweigh the costs of the combined treatment. We hypothesize that side effects with adjunct aripiprazole (extrapyramidal side effects, weight gain and others) will not differ from placebo. We will estimate the additional costs and assess the relationship of adjunctive aripiprazole use with the perceived tolerability of continued use of risperidone (or paliperidone).

  • To evaluate the mediator effects of estrogen, progesterone, prolactin effects on quality of life, bone turnover and sexual functioning. [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    We will measure hormonal levels in blood and saliva to see the effects of treatment and improvements in symptoms. In exploratory analyses, we will examine the relationship of sex hormone changes to various outcomes. Sex hormone levels may predict improvement and serve as a biomarker for predicting outcome or bone turnover and determining optimal aripiprazole dose for individual patients. For example, women who have return of menses but do not ovulate, as evidenced by lack of luteal progesterone surge, may have less improvement in bone turnover and sexual side effects.


Estimated Enrollment: 80
Study Start Date: January 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aripiprazole Drug: Aripiprazole
Aripiprazole dosing will begin at 5 mg/day once daily and increased to 10mg by mouth once daily at the end of week 2 and then increased to 15 mg/day once daily at the end of week 8 in women who have not yet regained their menstrual period. If a woman gets her menstrual period on the 5 or 10 mg dose she will remain on this dose for the study.
Other Name: Abilify
Placebo Comparator: Placebo Drug: Placebo
The placebo will be sucrose filled capsules that are identical to the active medication. It is double blind so no one will know if the capsule is placebo or aripiprazole.

Detailed Description:

This will be a 16-week, double blind, placebo controlled randomized trial of aripiprazole added to an existing stabilized regimen of antipsychotics (either risperidone or paliperidone oral or long acting injectable formulations) for treatment of elevated symptomatic prolactin levels. Aripiprazole dosing will begin at 5 mg/day once daily and increased to 10mg by mouth once daily at the end of week 2 and then increased to 15 mg/day once daily at the end of week 8 in women who have not yet regained their menstrual period. If a woman gets her menstrual period on the 5 or 10 mg dose she will remain on this dose for the study. Women will remain on their current stabilized medication regimen during the course of the adjunctive trial of aripiprazole or placebo. Subjects will be able to receive anticholinergic medications as needed (e.g., benztropine and diphenhydramine) for extrapyramidal side effects, propranolol for akathisia, and benzodiazepines (e.g.,lorazepam) for agitation or anxiety.

Participants will be assigned to either get aripiprazole or placebo (a sugar pill), this will be decided randomly with a 50-50 chance of receiving one or the other medication. The placebo will be sucrose filled capsules that are identical to the active medication. It is double blind so no one will know if the capsule is placebo or aripiprazole. The dosing will be the exact same, one capsule taken daily until week 8. At this time 2 capsules will be given if the participant dose not regains their menstrual period.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects will be females of any race, with an age range of 18?50.
  • Subjects will meet DSM-IV TR (APA, 2000) criteria for either schizophrenia or schizoaffective disorder. A best estimate diagnostic approach will be utilized in which information from the Structured Clinical Interview for DSM-IV (First et al, 1997) is supplemented by information from family informants, previous psychiatrists, and medical records to generate a diagnosis.
  • Women will need to be taking a stable dose of antipsychotic regimen for at least two months and are considered to have stable symptoms by the treating psychiatrist. This regimen must include any form of risperidone or paliperidone.
  • All women will have a prolactin level > 24 ng/ml (either identified at screening or from the past 6 weeks in the medical record)
  • All women will have evidence of a prolactin related hormonal side effect (amenorrhea, oligomenorrhea or galactorrhea). This will be determined by patient report/history and medical record/clinician interview. Oligomenorrhea is defined as infrequent, irregularly timed episodic bleeding occurring at intervals of more than 35 days from the previous menstrual cycle and amenorrhea is defined as absence of menstruation for three menstrual cycles or 6 months (Berek et al. 2002). Galactorrhea is defined as lactation or copious milk secretion.
  • Subjects must be judged competent to participate in the informed consent process and provide voluntary informed consent, by scoring a 10 out of 12 on the Evaluation to Sign Consent (ESC)

Exclusion Criteria:

  • Postmenopausal women will be excluded. Since it may be difficult to determine menopause in patients with amenorrhea, any women more than 45 years will be assessed for menopausal symptoms such as but not limited to or by: hot flushes, depression, excitability and fatigue. A medical doctor will advise on the menopausal status.
  • Patients with a history of a pituitary tumor (microadenoma, macroadenoma, neoplasm) will not be included in the study. Previous medical records will be obtained if possible to examine prolactin levels and medical histories.
  • Subjects with documented Cushing's disease, or who are pregnant or currently lactating post pregnancy will be excluded.
  • Subjects who meet DSM-IV TR criteria for alcohol or substance abuse within the last month are excluded. Subjects with nicotine use or dependence will not be excluded.
  • Medications which may increase prolactin or cause sexual dysfunction, including: metoclopramide, methyldopa, reserpine, amoxapine, droperidol, prochlorperazine, promethazine, bromocriptine, cabergoline, pergolide, There are many medications that may affect sexual function (not hormonal side effects) unrelated to dopamine transmission. These are only permitted as long as the subject has been receiving them for greater than 4 weeks (SSRIs, mood stabilizers, diuretics, antihypertensives, H2antagonists, bupropion). We allow these medications to enhance generalizability
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01338298

Contacts
Contact: Ann Kearns 410-402-6854 akearns@mprc.umaryland.edu
Contact: Stephanie Feldman 410-402-6885 sfeldman@mprc.umaryland.edu

Locations
United States, Maryland
Maryland Psychiatric Research Center Recruiting
Catonsville, Maryland, United States, 21228
Principal Investigator: Deanna L. Kelly, Pharm.D., BCPP         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Deanna L Kelly, Pharm.D., BCPP University of Maryland
  More Information

No publications provided

Responsible Party: MPRC, Deanna L. Kelly, Pharm.D., BCPP, University of Maryland
ClinicalTrials.gov Identifier: NCT01338298     History of Changes
Other Study ID Numbers: HP-00047496, HP-00055154
Study First Received: April 17, 2011
Last Updated: October 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
Schizophrenia
Symptomatic Hyperprolactinemia
Hormone
Menstrual

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Hyperprolactinemia
Hyperpituitarism
Aripiprazole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on October 01, 2014