Trial Outcomes & Findings for Minocycline Augmentation to Clozapine (NCT NCT02124811)
NCT ID: NCT02124811
Last Updated: 2018-09-26
Results Overview
Positive symptoms (representing unusual thought content) of schizophrenia/schizoaffective disorder were measured with the positive subscale of the Positive and Negative Syndrome Scale (PANSS). The PANSS is scored by the clinician-researcher after an interview with the patient and it is the most commonly used measure for assessing the symptoms of schizophrenia. Seven items measure the positive symptoms of delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The items are scored on a scale of 1 to 7 where 1 means the symptom is absent and 7 means the symptom is extreme. The total summed score for the positive subscale ranges between 7 and 49 where higher scores indicate more severe symptoms. A reduction in the score indicates an improvement in symptom severity.
COMPLETED
PHASE4
10 participants
Baseline, Week 12
2018-09-26
Participant Flow
Participants were recruited between February 2015 and November 2016 from the Persistent Symptoms: Treatment, Assessment and Recovery (PSTAR) Clinic at Grady Memorial Hospital in Atlanta, Georgia.
Eighteen individuals were screened and 8 of these did not meet eligibility criteria or were lost to follow up prior to beginning the study treatment, resulting in 10 participants who began treatment.
Participant milestones
| Measure |
High CRP
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
|
Overall Study
COMPLETED
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
High CRP
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Overall Study
Early termination
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Minocycline Augmentation to Clozapine
Baseline characteristics by cohort
| Measure |
High CRP
n=5 Participants
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=5 Participants
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Tumor Necrosis Factor (TNF) Alpha
|
6.07 pg/ml
STANDARD_DEVIATION 2.29 • n=5 Participants
|
5.36 pg/ml
STANDARD_DEVIATION 2.88 • n=7 Participants
|
5.71 pg/ml
STANDARD_DEVIATION 2.48 • n=5 Participants
|
|
Interleukin 1 (IL-1) beta
|
0.62 pg/ml
STANDARD_DEVIATION 0.20 • n=5 Participants
|
0.73 pg/ml
STANDARD_DEVIATION 0.22 • n=7 Participants
|
0.67 pg/ml
STANDARD_DEVIATION 0.21 • n=5 Participants
|
|
Interleukin 6 (IL-6)
|
3.12 pg/ml
STANDARD_DEVIATION 4.29 • n=5 Participants
|
1.11 pg/ml
STANDARD_DEVIATION 0.21 • n=7 Participants
|
2.12 pg/ml
STANDARD_DEVIATION 3.05 • n=5 Participants
|
|
Interleukin 10 (IL-10)
|
0.64 pg/ml
STANDARD_DEVIATION 0.56 • n=5 Participants
|
0.23 pg/ml
STANDARD_DEVIATION 0.13 • n=7 Participants
|
0.44 pg/ml
STANDARD_DEVIATION 0.44 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Participants who completed the study are included in this analysis.
Positive symptoms (representing unusual thought content) of schizophrenia/schizoaffective disorder were measured with the positive subscale of the Positive and Negative Syndrome Scale (PANSS). The PANSS is scored by the clinician-researcher after an interview with the patient and it is the most commonly used measure for assessing the symptoms of schizophrenia. Seven items measure the positive symptoms of delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The items are scored on a scale of 1 to 7 where 1 means the symptom is absent and 7 means the symptom is extreme. The total summed score for the positive subscale ranges between 7 and 49 where higher scores indicate more severe symptoms. A reduction in the score indicates an improvement in symptom severity.
Outcome measures
| Measure |
High CRP
n=2 Participants
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=3 Participants
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Positive Subscale Score of the Positive and Negative Syndrome Scale (PANSS)
Baseline
|
22 units on a scale
Standard Deviation 7.07
|
22.33 units on a scale
Standard Deviation 1.53
|
|
Positive Subscale Score of the Positive and Negative Syndrome Scale (PANSS)
Week 12
|
16 units on a scale
Standard Deviation 5.66
|
20.33 units on a scale
Standard Deviation 4.73
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: Participants who completed the study are included in this analysis.
Negative symptoms (representing a loss of normal functions) of schizophrenia/schizoaffective disorder were measured with the negative subscale of the Positive and Negative Syndrome Scale (PANSS). The PANSS is scored by the clinician-researcher after an interview with the patient and it is the most commonly used measure for assessing the symptoms of schizophrenia. Seven items measure the negative symptoms of blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity \& flow of conversation, and stereotyped thinking. The items are scored on a scale of 1 to 7 where 1 means the symptom is absent and 7 means the symptom is extreme. The total summed score for the negative subscale ranges between 7 and 49 where higher scores indicate more severe symptoms. A reduction in the score indicates an improvement in symptom severity.
Outcome measures
| Measure |
High CRP
n=2 Participants
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=3 Participants
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Negative Subscale Score of the Positive and Negative Syndrome Scale (PANSS)
Baseline
|
17 units on a scale
Standard Deviation 12.73
|
22.67 units on a scale
Standard Deviation 5.77
|
|
Negative Subscale Score of the Positive and Negative Syndrome Scale (PANSS)
Week 12
|
16.5 units on a scale
Standard Deviation 3.54
|
22.33 units on a scale
Standard Deviation 2.08
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: This analysis includes participants who completed the study and who completed the BACS. One participant in the high CRP did not complete this test at either time point.
The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcomes in patients with schizophrenia (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, and executive function). BACS takes less than 35 minutes to complete and was administered on an electronic tablet for this study. The composite score is a T-score that averages the standardized scale scores of each of the six tests. The composite T-score has a mean of 50 and a standard deviation of 10. Scores below 50 indicate lower than average cognition while scores above 50 indicate higher than average cognition. A prior study found that the BACS mean composite score for schizophrenia patients was 25.96 while healthy controls had a mean score of 47.00.
Outcome measures
| Measure |
High CRP
n=1 Participants
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=3 Participants
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Brief Assessment of Cognition in Schizophrenia (BACS) Score
Baseline
|
36 units on a scale
Standard Deviation 0
|
31.33 units on a scale
Standard Deviation 16.29
|
|
Brief Assessment of Cognition in Schizophrenia (BACS) Score
Week 12
|
42 units on a scale
Standard Deviation 0
|
28 units on a scale
Standard Deviation 13.00
|
PRIMARY outcome
Timeframe: Baseline, Week 12General symptoms of schizophrenia/schizoaffective disorder were measured using the general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS). The PANSS is scored by the clinician-researcher after an interview with the patient and it is the most commonly used measure for assessing the symptoms of schizophrenia. Sixteen items measure general psychopathology symptoms of somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Items are scored on a scale of 1 to 7 where 1 means the symptom is absent and 7 means the symptom is extreme. Total scores for this subscale can range from 16 to 112 where higher scores indicate more severe symptoms. A reduction in the score indicates an improvement in symptom severity.
Outcome measures
| Measure |
High CRP
n=1 Participants
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=3 Participants
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
General Psychopathology Score of the Positive and Negative Syndrome Scale (PANSS)
Baseline
|
33 units on a scale
Standard Deviation 0.0
|
36 units on a scale
Standard Deviation 7.55
|
|
General Psychopathology Score of the Positive and Negative Syndrome Scale (PANSS)
Week 12
|
27 units on a scale
Standard Deviation 0.0
|
37 units on a scale
Standard Deviation 9.17
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Participants who completed the study are included in this analysis
Perceived quality of life and general well being was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). The Q-LES-Q-SF is a 16-item questionnaire asking participants to rate how satisfied they have been with heath related qualities on a 5-point scale where 1 = very poor and 5 = very good. Raw scores of the Q-LES-Q-SF range from 14 to 70 and higher scores indicate higher life enjoyment and satisfaction.
Outcome measures
| Measure |
High CRP
n=2 Participants
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=3 Participants
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Score
Baseline
|
47.5 units on a scale
Standard Deviation 3.54
|
64 units on a scale
Standard Deviation 14
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Score
Week 12
|
53.5 units on a scale
Standard Deviation 10.61
|
65.67 units on a scale
Standard Deviation 15.63
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: A protocol amendment removed the GAF outcome measure as this information was determined to be non-essential. To reduce participant burden, data were not collected for this outcome measure.
Social, occupational, and psychological functioning was to be assessed using the Global Assessment of Functioning (GAF) in the initial study protocol.
Outcome measures
Outcome data not reported
Adverse Events
High CRP
Low CRP
Serious adverse events
| Measure |
High CRP
n=5 participants at risk
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=5 participants at risk
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Gastrointestinal disorders
Hospitalization due to ischemic colitis
|
0.00%
0/5 • Information on adverse events was collected from the time when participants begin taking the study medication until completion of study participation (after participants had taken the study medication for 12 weeks).
Adverse Events and side effects were asked about using a Side Effect Checklist, which asks about common side effects of clozapine and minocycline and allow for an open ended question to capture any unanticipated adverse events.
|
20.0%
1/5 • Number of events 1 • Information on adverse events was collected from the time when participants begin taking the study medication until completion of study participation (after participants had taken the study medication for 12 weeks).
Adverse Events and side effects were asked about using a Side Effect Checklist, which asks about common side effects of clozapine and minocycline and allow for an open ended question to capture any unanticipated adverse events.
|
|
Psychiatric disorders
Inpatient psychiatric hospitalization
|
0.00%
0/5 • Information on adverse events was collected from the time when participants begin taking the study medication until completion of study participation (after participants had taken the study medication for 12 weeks).
Adverse Events and side effects were asked about using a Side Effect Checklist, which asks about common side effects of clozapine and minocycline and allow for an open ended question to capture any unanticipated adverse events.
|
40.0%
2/5 • Number of events 2 • Information on adverse events was collected from the time when participants begin taking the study medication until completion of study participation (after participants had taken the study medication for 12 weeks).
Adverse Events and side effects were asked about using a Side Effect Checklist, which asks about common side effects of clozapine and minocycline and allow for an open ended question to capture any unanticipated adverse events.
|
Other adverse events
| Measure |
High CRP
n=5 participants at risk
Participants with treatment resistant schizophrenia and a high baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values greater than 3 milligrams per liter (mg/L) of blood are considered high.
|
Low CRP
n=5 participants at risk
Participants with treatment resistant schizophrenia and a low baseline C-reactive protein (CRP) level received minocycline augmentation with clozapine. CRP levels were measured by a high sensitivity CRP test (hs-CRP) and baseline values equal to or less than 3 milligrams per liter (mg/L) of blood are considered low.
|
|---|---|---|
|
Vascular disorders
Hypotension
|
0.00%
0/5 • Information on adverse events was collected from the time when participants begin taking the study medication until completion of study participation (after participants had taken the study medication for 12 weeks).
Adverse Events and side effects were asked about using a Side Effect Checklist, which asks about common side effects of clozapine and minocycline and allow for an open ended question to capture any unanticipated adverse events.
|
20.0%
1/5 • Number of events 1 • Information on adverse events was collected from the time when participants begin taking the study medication until completion of study participation (after participants had taken the study medication for 12 weeks).
Adverse Events and side effects were asked about using a Side Effect Checklist, which asks about common side effects of clozapine and minocycline and allow for an open ended question to capture any unanticipated adverse events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place