Trial Outcomes & Findings for Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis (NCT NCT01132118)
NCT ID: NCT01132118
Last Updated: 2014-09-03
Results Overview
We will examine the effect of HCQ on the Matsuda Insulin Sensitivity Index (ISI) during the active treatment phase compared with placebo phase. ISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as follows: ISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean G0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
30 participants
Primary outcome timeframe
Baseline and Week 8
Results posted on
2014-09-03
Participant Flow
107 potentially eligible RA patients were screened during 2010-2011. 7 subjects did not meet inclusion/exclusion criteria at screening and 63 declined participation.
37 subjects were initially consented, 7 withdrew consent before randomization. Thirty patients were randomized. Five patients withdrew consent after randomization and two patients stopped participation in the study due to non-serious adverse events.
Participant milestones
| Measure |
HCQ Then Placebo
This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo Then HCQ
This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
|---|---|---|
|
First Intervention (8 Weeks)
STARTED
|
15
|
15
|
|
First Intervention (8 Weeks)
COMPLETED
|
12
|
12
|
|
First Intervention (8 Weeks)
NOT COMPLETED
|
3
|
3
|
|
Second Intervention (8 Weeks)
STARTED
|
12
|
12
|
|
Second Intervention (8 Weeks)
COMPLETED
|
12
|
11
|
|
Second Intervention (8 Weeks)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
HCQ Then Placebo
This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo Then HCQ
This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
|---|---|---|
|
First Intervention (8 Weeks)
Adverse Event
|
1
|
0
|
|
First Intervention (8 Weeks)
Withdrawal by Subject
|
2
|
3
|
|
Second Intervention (8 Weeks)
Adverse Event
|
0
|
1
|
Baseline Characteristics
Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
HCQ Then Placebo
n=15 Participants
This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo Then HCQ
n=15 Participants
This arm of the study contains half the study population after randomization. The participants in this arm received hydroxychloroquine for 8 weeks and then crossed over to a placebo for 8 weeks. Study staff was blinded to which order they were taking the hydroxychloroquine and placebo in.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56 years
STANDARD_DEVIATION 14 • n=5 Participants
|
57 years
STANDARD_DEVIATION 14 • n=7 Participants
|
56.5 years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 8We will examine the effect of HCQ on the Matsuda Insulin Sensitivity Index (ISI) during the active treatment phase compared with placebo phase. ISI is based on insulin and glucose levels in a fasting state during an oral glucose tolerance test (OGTT) and is calculated as follows: ISI (Matsuda) = 10000/√ G0 X I0 X Gmean X Imean G0 - fasting plasma glucose (mg/dL) I0 - fasting plasma insulin (mIU/L) Gmean - mean plasma glucose during OGTT (mg/dL) Imean - mean plasma insulin during OGTT (mIU/L)
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
Insulin Sensitivity Index
Baseline
|
7.7 (dL x L)/(mg x mIU)
Standard Deviation 4.8
|
7.7 (dL x L)/(mg x mIU)
Standard Deviation 4.8
|
|
Insulin Sensitivity Index
Period Value
|
8.1 (dL x L)/(mg x mIU)
Standard Deviation 4.5
|
7.8 (dL x L)/(mg x mIU)
Standard Deviation 4.0
|
|
Insulin Sensitivity Index
Change
|
0.4 (dL x L)/(mg x mIU)
Standard Deviation 2.9
|
0.14 (dL x L)/(mg x mIU)
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: Baseline and Week 8We will examine the effect of HCQ on HOMA-IR during the active treatment phase compared with placebo phase. HOMA-IR = (Glucose x insulin)/405
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
HOMA-IR
Baseline
|
2.0 (mg x mIU)/(dL*L)
Standard Deviation 1.7
|
2.0 (mg x mIU)/(dL*L)
Standard Deviation 1.7
|
|
HOMA-IR
Period
|
1.7 (mg x mIU)/(dL*L)
Standard Deviation 1.0
|
1.6 (mg x mIU)/(dL*L)
Standard Deviation 0.79
|
|
HOMA-IR
Change
|
-0.3 (mg x mIU)/(dL*L)
Standard Deviation 1.5
|
-0.42 (mg x mIU)/(dL*L)
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: Baseline and Week 8HOMA-B = (360 x Insulin)/(Glucose - 63)
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
HOMA-B
Baseline
|
116.5 (mIU x dL)/(L x mg)
Standard Deviation 100.4
|
116.5 (mIU x dL)/(L x mg)
Standard Deviation 100.4
|
|
HOMA-B
Period
|
110.8 (mIU x dL)/(L x mg)
Standard Deviation 81.6
|
109.7 (mIU x dL)/(L x mg)
Standard Deviation 82.6
|
|
HOMA-B
Change
|
-5.8 (mIU x dL)/(L x mg)
Standard Deviation 72.9
|
-6.8 (mIU x dL)/(L x mg)
Standard Deviation 78.0
|
SECONDARY outcome
Timeframe: Baseline and Week 8mg/dL
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
Total Cholesterol
Baseline
|
192.4 mg/dL
Standard Deviation 37.5
|
192.4 mg/dL
Standard Deviation 37.5
|
|
Total Cholesterol
Period
|
179.7 mg/dL
Standard Deviation 44.3
|
189.4 mg/dL
Standard Deviation 37.9
|
|
Total Cholesterol
Change
|
-12.7 mg/dL
Standard Deviation 20.0
|
-3.0 mg/dL
Standard Deviation 22.4
|
SECONDARY outcome
Timeframe: Baseline and Week 8mg/dL
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
LDL Cholesterol
Baseline
|
114.1 mg/dL
Standard Deviation 29.8
|
114.1 mg/dL
Standard Deviation 29.8
|
|
LDL Cholesterol
Period
|
101.7 mg/dL
Standard Deviation 36.7
|
109.9 mg/dL
Standard Deviation 33.1
|
|
LDL Cholesterol
Change
|
-12.4 mg/dL
Standard Deviation 20.1
|
-4.2 mg/dL
Standard Deviation 17.7
|
SECONDARY outcome
Timeframe: Baseline and Week 8mg/dL
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
HDL Cholesterol
Baseline
|
58.1 mg/dL
Standard Deviation 17.9
|
58.1 mg/dL
Standard Deviation 17.9
|
|
HDL Cholesterol
Period
|
59.4 mg/dL
Standard Deviation 18.2
|
60.3 mg/dL
Standard Deviation 17.8
|
|
HDL Cholesterol
Change
|
1.3 mg/dL
Standard Deviation 6.7
|
2.2 mg/dL
Standard Deviation 9.8
|
SECONDARY outcome
Timeframe: Baseline and Week 8mg/dL
Outcome measures
| Measure |
Hydroxychloroquine
n=23 Participants
This group contains results for when study participants were taking hydroxychlorquine.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided was based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
Placebo
n=23 Participants
This arm group contains the results for patients while they were on placebo.
|
|---|---|---|
|
Triglycerides
Baseline
|
100.6 mg/dL
Standard Deviation 44.0
|
100.6 mg/dL
Standard Deviation 44.0
|
|
Triglycerides
Period
|
92.4 mg/dL
Standard Deviation 41.7
|
95.6 mg/dL
Standard Deviation 44.9
|
|
Triglycerides
Change
|
-8.2 mg/dL
Standard Deviation 45.0
|
-5.0 mg/dL
Standard Deviation 20.1
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Hydroxychloroquine
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=15 participants at risk
Participants received Placebo tablets for 8 weeks.
|
Hydroxychloroquine
n=15 participants at risk
Participants received hydroxychloroquine (HCQ) for 8 weeks.
Hydroxychloroquine: Hydroxychloroquine comes in 200 mg tablets and is taken orally. The dose provided will be based upon a calculation of 6.5 mg/kg (subject's weight), which is the dose range commonly used to treat rheumatoid arthritis and lupus. Dosages will be rounded to the nearest 100 mg.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Liver Function Test Abnormality
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place