Primary outcome
What APPLE measured first
| Controln=16 | PCOS Medication Naiven=30 | PCOS, Medication Naive + Byettan=9 | PCOS on COCPsn=8 | PCOS on Metforminn=4 |
|---|---|---|---|---|
| 1.85(1.24) | 1.46(0.21) | 1.54(0.38) | 1.88(0.49) | 1.57(0.07) |
Phase 2 and Phase 3 · Exenatide
APPLE trial results
Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls
Hepatic Glucose Release (mg/kg/min), Measured up to 4 months from enrollment. Control: 1.85; PCOS Medication Naive: 1.46; PCOS, Medication Naive + Byetta: 1.54; PCOS on COCPs: 1.88; PCOS on Metformin: 1.57.
- Participants
- 92
- Status
- completed
- Completed
- 2022-12
- Sponsor
- University of Colorado, Denver
As posted on ClinicalTrials.gov (NCT02157974), updated at source Jun 4, 2024. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Secondary outcomes
What else it measured
| Measure | Controln=5 | PCOS Medication Naiven=0 | PCOS, Medication Naive + Byettan=8 | PCOS on COCPsn=9 | PCOS on Metforminn=6 |
|---|---|---|---|---|---|
| PDE/TP | 0.167684728(0.056413082) | not reported | 0.198640255(0.040933351) | 0.198787476(0.045832565) | 0.186923469(0.039481266) |
| PME/TP | 0.067905319(0.033816456) | not reported | 0.077949656(0.02943916) | 0.075872089(0.024970918) | 0.066789803(0.036986035) |
| ATP/TP | 0.592517535(0.038294886) | not reported | 0.566952309(0.061717281) | 0.565157308(0.042119495) | 0.557277652(0.034367129) |
| Pi/TP | 0.041945761(0.02076513) | not reported | 0.054581135(0.019288097) | 0.046604505(0.022669904) | 0.074459672(0.021584936) |
| NADPH/TP | 0.097201285(0.043438464) | not reported | 0.068550332(0.028503778) | 0.067305736(0.033620062) | 0.074693726(0.021031863) |
| UDPG/TP | 0.032745372(0.011777685) | not reported | 0.033326313(0.014030497) | 0.046272886(0.023894603) | 0.039855678(0.012418624) |
| Controln=18 | PCOS Medication Naiven=32 | PCOS, Medication Naive + Byettan=10 | PCOS on COCPsn=10 | PCOS on Metforminn=6 |
|---|---|---|---|---|
| 0.54(0.17) | 0.49(0.22) | 0.49(0.24) | 0.78(0.18) | 0.65(0.19) |
| Controln=24 | PCOS Medication Naiven=40 | PCOS, Medication Naive + Byettan=10 | PCOS on COCPsn=10 | PCOS on Metforminn=6 |
|---|---|---|---|---|
| 4.1(3.1) | 7.6(6.3) | 6.9(5.3) | 6.8(9.4) | 13.3(12.1) |
| Controln=9 | PCOS Medication Naiven=12 | PCOS, Medication Naive + Byettan=10 | PCOS on COCPsn=5 | PCOS on Metforminn=3 |
|---|---|---|---|---|
| 9.3(5.3) | 6.6(4.2) | 7.9(7.2) | 18.2(14.9) | 19.4(17.4) |
The trial
How APPLE was run
Women with polycystic ovarian syndrome (PCOS) have increased rates of hepatic steatosis compared to weight similar women with regular menses. It is unclear if this is related to high testosterone or insulin resistance. The investigators will assess hepatic glucose release, rates of lipolysis and hepatic de novo lipogenesis in the fasted and postprandial state to determine if alterations in the processes contribute to hepatic steatosis. Participants will be overweight, sedentary girls with or without PCOS. Those with PCOS will either be medication naive, or must be taking metformin or combined oral contraceptives (COCPs) for a period of at least 6 months prior to study procedures.
- PCOS, medication naive + Byetta: PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.
- Control: Up to 25 girls without PCOS
- PCOS medication naive: Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.
- PCOS on COCPs: Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.
- PCOS on metformin: Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Who could join the trial
Inclusion Criteria: * Females * 2 years post-menarche * BMI percentile \>90% Exclusion Criteria: * Type 2 diabetes * Anemia * Liver disease * Medications known to effect insulin sensitivity * Cause of oligomenorrhea or hirsutism other than PCOS, * \>3 hours a week of moderate exercise.
Published papers
Papers from APPLE
- Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108.
- Carreau AM, Pyle L, Garcia-Reyes Y, Rahat H, Vigers T, Jensen T, Scherzinger A, Nadeau KJ, Cree-Green M. Clinical prediction score of nonalcoholic fatty liver disease in adolescent girls with polycystic ovary syndrome (PCOS-HS index). Clin Endocrinol (Oxf). 2019 Oct;91(4):544-552. doi: 10.1111/cen.14062. Epub 2019 Aug 16.
- Simon SL, McWhirter L, Diniz Behn C, Bubar KM, Kaar JL, Pyle L, Rahat H, Garcia-Reyes Y, Carreau AM, Wright KP, Nadeau KJ, Cree-Green M. Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3525-3534. doi: 10.1210/jc.2018-02385.
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
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