| Authors |
Date |
Country |
Study Design |
Statistical technique |
Outcome |
Intervention Group (IG) |
Control Group (CG) |
Methodological Quality |
| Johansson, BL, Sjoberg S, Wahren J (Study 1) |
1992 |
Sweden |
Controlled Trial |
Paired t-test, Wilcoxon's signed rank test and analyses of variance. |
GFR |
Basal (n=11): 143 ± 4
Low-dose (n=11): 133 ± 4
High-dose (n=7): 132 ± 4 |
Basal (n=10): 132 ± 4
60 min (n=10): 130 ± 4
120 min (n=10): 127 ± 3 |
5 |
| |
ERPF |
IG
Basal (n=11): 741 ± 34
Low-dose (n=11): 760 ± 35
High-dose (n=7): 791 ± 34 |
CG
Basal (n=10): 708 ± 22
60 min (n=10):728 ± 23
120 min (n=10):725 ± 28 |
|
| FF |
Basal (n=11):19.3 ± 0.5
Low-dose (n=11):17.6 ± 0.5
High-dose (n=7):16.8 ± 0.3 |
Basal (n=10):18.8 ± 0.7
60 min (n=10):17.9 ± .6
120 min (n=10):17.2 ± 0.7 |
|
| PAH extraction |
Basal (n=11): 90 ± 1
Low-dose (n=11): 92 ± 2
High-dose (n=7):91 ± 3 |
Basal (n=10):90 ± 1
60 min (n=10):90 ± 1
120 min (n=10):91 ± 1 |
|
| Johansson, BL, Kernell A, Sjoberg S, Wahren J
(Study 2) |
1993 |
Sweden |
Double-blind, randomised control trial |
Student’s t test and Wilcoxon’s sign rank test. |
GFR |
Basal: 147 ± 5
2 weeks: 138 ± 6
4 weeks: 138 ± 6 |
Basal: 142 ± 6
2 weeks: 141 ± 6
4 Weeks: 142 ± 5 |
6 |
| |
ERPF |
Basal: 734 ± 65
2 weeks: 715 ± 53
4 weeks: 663 ± 29 |
Basal: 634 ± 47
2 weeks: 575 ± 77
4 weeks: 611 ± 44 |
|
| FF |
Basal: 21 ± 2
2 weeks: 20 ± 2
4 weeks: 21 ± 1 |
Basal: 23 ± 1
2 weeks: 27 ± 3
4 weeks: 24 ± 2 |
|
| UAE |
Basal: 21 ± 6
2 weeks: 12 ± 2
4 weeks: 9 ± 1 |
Data not given but states
unchanged |
|
| Johansson BL, Borg K, Fernqvist-Forbes E, Odergren T, Remahl S, Wahren J
(Study 3) |
1996 |
Sweden |
Double-blind, randomised, cross-over, controlled trial |
As means ± SEM. Statistical tests:student’s t test, signed rank test, Wilcoxon’s sum rank test Wilcoxon’s matched pairs. P values <0.05 statistically significant. |
Change in vibratory threshold |
(n=8): 2 ± 11 |
(n=8): -4 ± 8 |
6 |
| Heart rate variability |
Basal (n=11): 13 ± 1
During infusion (n=11): 20
± 2 |
Basal (n=11):14 ± 2
During infusion (n=11):
15 ± 2 |
| Brake Index during tilting |
Basal (n=7): 4.6 ± 1.0
Infusion: 10.3 ± 2.2 |
Basal (n=7): 5.9 ± 2.5
Infusion: 4.1 ± 1.1 |
| Acceleration Index during tilting |
Basal (n=4): 8.2 ± 0.9
Infusion: 14.5 ± 4.8 |
Basal (n=4): 8.5 ± 2.5
Infusion: 9.3 ± 1.9 |
| Warm-cold difference |
(n=8): 9 ± 6 |
(n=8): -2 ± 4 |
| Heat pain threshold |
(n=8): 1 ± 1 |
(n=8): 0 ± 1 |
| Johansson BL, Borg K, Fernqvist-Forbes E, Kernell A, Odergren T, Wahren, J
(Study 4) |
2000 |
Sweden |
Double-blind, randomised, multi-centre, cross-over, controlled trial |
As means ± SEM. Geometric means used for UAE and albumin/
creatinine excretion. Student’s t test and Wilcoxon’s matched-pair test used to evaluate autonomic and sensory nerve function. |
AER |
GROUP 1
(n=10)
Baseline: 56
1 month: 46
2 month: 47
3 month: 37
GROUP 2
(n=11)
4 month: 54
5 month: 36 |
GROUP 1
(n=10)
4 month: 46
5 month: 46
6 month: 51
GROUP 2
(n=11)
Baseline: 49
1 month: 49
2 month: 53
3 month: 60 |
6 |
| |
|
|
|
|
GFR |
GROUP 1
Baseline:
106 ± 6
Month 3: 105 ± 5
GROUP 2
Month 6: 108 ± 3 |
GROUP 1
Month 6: 101 ± 6
GROUP 2
Baseline: 111 ± 3
Month 3: 111 ± 5 |
|
| |
|
|
|
|
Heart rate variability |
(n=12)
Baseline: 18 ± 2
After C-peptide: 21 ± 1 |
(n=12)
Baseline:
19 ± 1
After placebo: 16 ± 1 |
|
| |
|
|
|
|
Vibratory Threshold |
(n=6)
Baseline: 7.0 ± 2.3
3/12
C-peptide: 9.4 ± 3.0 |
(n=6)
Baseline:
7.9 ± 3.0
3/12
placebo: 7.5 ± 2.2 |
|
| |
|
|
|
|
Heat-pain threshold |
(n=6)
Baseline: 47.6 ± 0.8
3/12 C-peptide: 49.9 ± 1.3 |
(n=6)
Baseline: 48.1 ± 0.8
3/12 placebo: 48.0 ± 0.6 |
|
| |
|
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|
|
Brake and acceleration indices |
Break indices tended to improve with C-peptide (P<0.1). The acceleration index improved in one of the two patients. |
Both indices were unchanged during placebo treatment |
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| |
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|
Postural hypotension |
Both patients with postural hypotension prior to the study beginning tolerated the 8 minute tilting well with normal BP responses after C-peptide treatment. |
The same two patients became symptomatically hypotensive during tilting after 3/12 placebo treatment. |
|
| Ekberg K, Brismar T, Johansson B/L/. Jonsson B, Lindstrom P, Wahren J (Study 5) |
2003 |
Sweden |
Randomised, double blind, placebo controlled |
As mean ± SEM. Mann Whitney two to undertake comparison between groups. Wilcoxon’s signed rank test to compare between groups. |
|
|
|
8 |
| |
|
|
|
|
MCV |
(Baseline 44.9 ± 0.79)
6 weeks: 0.8 ± 0.32
12 weeks:0.1 ± 0.29 |
(Baseline: 67.7 ± 0.71)
6 weeks:0.3 ± 0.41
12 weeks:-0.7 ± 0.39 |
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| |
|
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|
CMAP |
(Baseline: 6.96 ± 0.50)
6 weeks: 0.4 ± 0.36
12 weeks:0.1 ± 0.29 |
(Baseline: 7.60 ± 0.41)
6 weeks: 0.4 ± 0.27
12 weeks: 0.2 ± 0.29 |
|
| |
|
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|
SCV |
Baseline: (50.5 ± 0.89)
6 weeks: 1.6 ± 0.76
12 weeks:2.7 ± 0.85 |
Baseline: (51.4 ± 1.12)
6 weeks: 0.6 ± 0.91
12 weeks:0.6 ± 0.80 |
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| |
|
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|
SNAP |
(Baseline: 16.3 ± 1.81)
6 weeks:0.6 ± 1.10
12 weeks: 0.7 ± 1.19 |
(Baseline: 15.8 ± 1.92)
6 weeks: 0.9 ± 0.95
12 weeks:3.4 ± 0.98 |
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| |
|
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|
Cold threshold |
(Baseline:3.4 ± 0.55)
12 weeks:0.3 ± 0.46 |
(Baseline:2.1 ± 0.17)
12 weeks: 0.2 ± 0.2 |
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| |
|
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|
|
Heat threshold |
Baseline: 8.0 ± 0.43
12 weeks: 0.3 ± 0.31 |
Baseline: 7.0 ± 0.47
12 weeks: 0.1 ± 0.26 |
|
| |
|
|
|
|
Vibration threshold |
Baseline: 0.63 ± 0.07
12 weeks: -0.2 ± 0.07 |
Baseline:0.48 ± 0.07
12 weeks: 0 ± 0.06 |
|
| Ekberg K, Brismar T, Johansson BL, Lindstrom P, Juntti-Berggren L, Norrby A, Berne C, Arnqvist HJ, Bolinder J, Wahren J
(Study 6) |
2007 |
Sweden |
Double-blind, randomised, placebo controlled, multi-centre |
As means ± SEM. Nerve conduction data in z-scores. QST as z-scores corrected for age. The Wilcoxon signed-rank:
compare baseline data and changes between and within groups. |
|
|
|
8 |
| |
|
|
|
|
SCVp |
Baseline: 35.4 ± 0.31
Low dose (n= 53): 0.38 ± 0.27
High dose (n=30):
0.63 ± 0.26
Active combined:
0.48 ± 0.19 |
Baseline: 35.4 ± 0.31
Placebo (n+47):
0.24 ± 0.27 |
|
| |
|
|
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|
SCVi |
Baseline: 44.2 ± 0.41
Low dose:0.77 ± 0.43
High dose: 1.14 ± 0.36
Active combined: 0.93 ± 0.29 |
Baseline: 44.2 ± 0.41
Placebo: 0.75 ± 0.38 |
|
| |
|
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|
MCV |
Baseline: 40.0 ± 0.41
Low dose: -0.25 ± 0.19
High dose:-0.57 ± 0.24
Active combined: -0.38 ± 0.15 |
Baseline:40.0 ± 0.41
Placebo: -0.53 ± 0.22 |
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| |
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|
z-VPT foot |
Baseline: 1.9 ± 0.12
Low dose: -0.07 ± 0.09
High dose: -0.12 ± 0.11
Active combined: -0.09 ± 0.07 |
Baseline: 1.9 ± 0.12
Placebo: 0.03 ± 0.13 |
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| |
|
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|
z-VPT lower leg |
Baseline: 0.6 ± 0.10
Low dose: -0.07 ± 0.09
High dose:-0.12 ± 0.11
Active combined: -0.19 ± 0.06 |
Baseline: 0.6 ± 0.10
Placebo:-0.09 ± 0.08 |
|
