Trial Outcomes & Findings for Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine (NCT NCT00512070)
NCT ID: NCT00512070
Last Updated: 2025-01-01
Results Overview
Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
40 participants
Primary outcome timeframe
6 and 12 weeks
Results posted on
2025-01-01
Participant Flow
Of the 40 participants who were initially consented, 5 were screen fails, 13 were lost to follow up and 5 were withdrawals prior to beginning Phase I of being prescribed olanzapine. 17 participants began Phase I and 4 were lost to follow up during that phase. 13 participants went on to Phase II to be randomized to one of two melatonin groups, however 3 were not able to collect data, leaving 10 participants in Phase II.
Participant milestones
| Measure |
Olanzapine Phase
In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day.
|
IIA (0.3mg/Day Melatonin)
In the 0.3mg/day melatonin in treatment phase II, all subjects will receive olanzapine (10-25mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin 0.3mg/day or 3mg/day. Group IIA will receive 0.3mg/day of melatonin.
|
IIB (3mg/Day Melatonin)
In the 3mg/day melatonin in treatment phase II, all subjects will receive olanzapine (10-25mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin 0.3mg/day or 3mg/day. Group IIB will receive 3mg/day of melatonin.
|
|---|---|---|---|
|
Phase I - Olanzapine Only
STARTED
|
17
|
0
|
0
|
|
Phase I - Olanzapine Only
COMPLETED
|
13
|
0
|
0
|
|
Phase I - Olanzapine Only
NOT COMPLETED
|
4
|
0
|
0
|
|
Phase II - Randomization to Melatonin
STARTED
|
0
|
6
|
7
|
|
Phase II - Randomization to Melatonin
COMPLETED
|
0
|
4
|
6
|
|
Phase II - Randomization to Melatonin
NOT COMPLETED
|
0
|
2
|
1
|
Reasons for withdrawal
| Measure |
Olanzapine Phase
In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day.
|
IIA (0.3mg/Day Melatonin)
In the 0.3mg/day melatonin in treatment phase II, all subjects will receive olanzapine (10-25mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin 0.3mg/day or 3mg/day. Group IIA will receive 0.3mg/day of melatonin.
|
IIB (3mg/Day Melatonin)
In the 3mg/day melatonin in treatment phase II, all subjects will receive olanzapine (10-25mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin 0.3mg/day or 3mg/day. Group IIB will receive 3mg/day of melatonin.
|
|---|---|---|---|
|
Phase I - Olanzapine Only
Lost to Follow-up
|
4
|
0
|
0
|
|
Phase II - Randomization to Melatonin
Data unable to be collected
|
0
|
2
|
1
|
Baseline Characteristics
Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
Baseline characteristics by cohort
| Measure |
IIA (0.3mg Day Melatonin)
n=4 Participants
0.3mg day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
IIB (3.0 mg/Day Melatonin)
n=6 Participants
3.0 mg/day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 6.61 • n=99 Participants
|
47.33 years
STANDARD_DEVIATION 12.58 • n=107 Participants
|
50.6 years
STANDARD_DEVIATION 10.97 • n=206 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=99 Participants
|
6 participants
n=107 Participants
|
10 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 6 and 12 weeksNocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
Outcome measures
| Measure |
IIA (0.3mg Day Melatonin)
n=4 Participants
0.3mg day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
IIB (3.0 mg/Day Melatonin)
n=6 Participants
3.0 mg/day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
|---|---|---|
|
Nocturnal Melatonin Production
Baseline
|
11.19 mg/dL
Standard Deviation 9.69
|
19.09 mg/dL
Standard Deviation 10.12
|
|
Nocturnal Melatonin Production
Week 6
|
10.39 mg/dL
Standard Deviation 8.51
|
15.18 mg/dL
Standard Deviation 12.49
|
|
Nocturnal Melatonin Production
Week 12
|
197.7 mg/dL
Standard Deviation 163.83
|
2,137.12 mg/dL
Standard Deviation 1,430.97
|
SECONDARY outcome
Timeframe: 6 weeks & 12 weeksweight (measured in kilograms)
Outcome measures
| Measure |
IIA (0.3mg Day Melatonin)
n=4 Participants
0.3mg day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
IIB (3.0 mg/Day Melatonin)
n=6 Participants
3.0 mg/day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
|---|---|---|
|
Weight
Baseline
|
87.10 kilograms
Standard Deviation 3.76
|
88.53 kilograms
Standard Deviation 24.99
|
|
Weight
Week 6
|
90.71 kilograms
Standard Deviation 3.65
|
93.20 kilograms
Standard Deviation 28.68
|
|
Weight
Week 12
|
93.45 kilograms
Standard Deviation 4.90
|
95.14 kilograms
Standard Deviation 28.71
|
SECONDARY outcome
Timeframe: 6 weeks & 12 weeksTotal cholesterol on metabolic blood panel
Outcome measures
| Measure |
IIA (0.3mg Day Melatonin)
n=4 Participants
0.3mg day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
IIB (3.0 mg/Day Melatonin)
n=6 Participants
3.0 mg/day melatonin
olanzapine and melatonin: In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
|
|---|---|---|
|
Total Cholesterol
Week 6
|
207 mg/dL
Standard Deviation 19.29
|
220.43 mg/dL
Standard Deviation 29.56
|
|
Total Cholesterol
Week 12
|
205.5 mg/dL
Standard Deviation 26.01
|
221.71 mg/dL
Standard Deviation 36.07
|
|
Total Cholesterol
Baseline
|
185.25 mg/dL
Standard Deviation 35.68
|
204.43 mg/dL
Standard Deviation 31.04
|
Adverse Events
Melatonin .3mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Melatonin 3mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Olanzapine Only
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Melatonin .3mg
n=4 participants at risk
After the olanzapine phase I, participants were randomized to receive a daily dose of melatonin at either .3mg or 3 mg.
|
Melatonin 3mg
n=6 participants at risk
After the olanzapine phase I, participants were randomized to receive a daily dose of melatonin at either .3mg or 3 mg.
|
Olanzapine Only
n=17 participants at risk
In phase one participants were prescribed olanzapine only
|
|---|---|---|---|
|
Psychiatric disorders
Psychiatric Hospitalization
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
Other adverse events
| Measure |
Melatonin .3mg
n=4 participants at risk
After the olanzapine phase I, participants were randomized to receive a daily dose of melatonin at either .3mg or 3 mg.
|
Melatonin 3mg
n=6 participants at risk
After the olanzapine phase I, participants were randomized to receive a daily dose of melatonin at either .3mg or 3 mg.
|
Olanzapine Only
n=17 participants at risk
In phase one participants were prescribed olanzapine only
|
|---|---|---|---|
|
General disorders
Abnormal lab values
|
50.0%
2/4 • Number of events 3
|
33.3%
2/6 • Number of events 2
|
29.4%
5/17 • Number of events 5
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
0.00%
0/17
|
|
Psychiatric disorders
Depression
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/17
|
|
General disorders
Headache
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
0.00%
0/17
|
|
Vascular disorders
Increased Blood Pressure
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
0.00%
0/17
|
|
Psychiatric disorders
Psychotic symptoms
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
|
General disorders
Somnolence
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
17.6%
3/17 • Number of events 3
|
|
Nervous system disorders
Tremors
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
0.00%
0/17
|
|
Psychiatric disorders
Anxiety/Agitation
|
0.00%
0/4
|
0.00%
0/6
|
11.8%
2/17 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4
|
0.00%
0/6
|
11.8%
2/17 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4
|
0.00%
0/6
|
17.6%
3/17 • Number of events 3
|
|
General disorders
Dry mouth
|
0.00%
0/4
|
0.00%
0/6
|
11.8%
2/17 • Number of events 2
|
|
General disorders
Flu symptoms
|
0.00%
0/4
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
|
Gastrointestinal disorders
Increased appetite
|
0.00%
0/4
|
0.00%
0/6
|
11.8%
2/17 • Number of events 2
|
|
General disorders
Insomnia/sleep disturbance
|
0.00%
0/4
|
0.00%
0/6
|
23.5%
4/17 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
0.00%
0/4
|
0.00%
0/6
|
11.8%
2/17 • Number of events 2
|
|
General disorders
Restless leg
|
0.00%
0/4
|
0.00%
0/6
|
11.8%
2/17 • Number of events 2
|
|
Reproductive system and breast disorders
Sexual dysfunction
|
0.00%
0/4
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/4
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/4
|
0.00%
0/6
|
5.9%
1/17 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place