Clinical trial NCT01325805: Efficacy of a Structured Weight Loss Program in Overweight Women With a History of Recurrent Pregnancy Loss
Official title: Pregnancy Outcomes in Overweight and Obese Women With a History of Recurrent Pregnancy Loss Randomized to a Structured Weight Loss Program Versus Routine Weight-Loss Counseling: A Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Obese
Overweight
Miscarriage
Recurrent Pregnancy Loss
Keywords: Miscarriage
Recurrent Pregnancy Loss
Obesity
Overweight
Diet
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2011-03-30
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Overweight and obesity has been associated with a number of adverse pregnancy outcomes in women of reproductive age, including infertility and early pregnancy loss. Recent data suggests that overweight and obese patients are also at increased risk of recurrent pregnancy loss (RPL), a devastating condition that affects 1% of the fertile population.

The investigators propose a prospective, randomized controlled trial in which overweight and obese patients with unexplained recurrent pregnancy loss are enrolled in a structured, 6 month, weight loss program or provided routine counseling regarding the importance of weight loss. Pregnancy outcomes will then be followed to assess miscarriage rates. Metabolic outcomes, such as lipid and glucose profiles, will also be evaluated.

Detailed description: The purpose of this study is to investigate the impact of a structured weight loss program versus traditional weight-loss counseling on pregnancy outcomes in women with recurrent pregnancy loss. The study protocol is as follows:

1. Patients will be notified of study via flyer inserted into patient chart at initial clinic visit, physician referral or Stanford website. Patients expressing interest will have their charts reviewed to confirm that they meet all enrollment criteria. Potential subjects will then be contacted via phone and verbal consent to participate obtained.
2. The participant will then have an office visit for consent signing and randomization. A formal weight will be obtained, the Beck Depression Inventory will be administered by Penny Donnelly, a self-administered questionnaire will be completed, and a basic laboratory evaluation, including a fasting lipid panel, alanine aminotransferase (ALT), fasting glucose and insulin levels, 2-hour glucose tolerance test, hemoglobin A1c and CRP will be preformed.
3. The patients will then be randomized to traditional weight loss counseling (control group) or to the structured weight loss program (study group). Patients will be instructed to discontinue attempts at conception.
4. Those patients randomized to the control group will receive the ACOG Patient Education pamphlets on obesity.
5. Those patients randomized to the study group will have a formal evaluation and counseling by Dr. Sun Kim, a medical endocrinologist specializing in weight management. They will then be enrolled in a structured weight loss program.
6. For all patients, a 3-month follow-up office visit will be scheduled. At this visit, a formal weight will be obtained, the Beck Depression Inventory will be re-administered by Penny Donnelly, a self-administered questionnaire will be completed, and a follow-up laboratory evaluation, including a fasting lipid panel, alanine aminotransferase (ALT), fasting glucose and insulin levels, 2-hour glucose tolerance test, hemoglobin A1c and CRP will be preformed. Patients will be informed that they may now being attempts to conceive.
7. Patients randomized to the study group will continue in the structured weight loss program for 6 months.
8. Six months after enrollment, all patients will have a telephone interview in which a close-out questionnaire will be administered and a final, self-reported weight will be obtained.
9. Primary and secondary outcomes will be followed for 2.5 years after date of enrollment for all patients.

Eligibility criteria: Inclusion Criteria:

1. Unexplained recurrent pregnancy loss (2 or more prior miscarriages)
2. BMI \>=25 kg/m2
3. Prepared to take 3 months ¡®time out¡± from attempting to conceive
4. Ability to attend a one hour initial, then 30 minute follow-up nutrition/monitoring session - once per week for one month, then every other week for 2 months, then once then once per month for 3 months.

Exclusion Criteria:

1. Age \>=40 years
2. Diagnosis of Type 1 or Type 2 Diabetes as defined by a fasting glucose \>=126, or 2 hour glucose \>=200 by a 75 gram oral glucose challenge
3. Presence of an endocrine condition such as hyperprolactinemia, Cushing¡-s syndrome or untreated thyroid disease (defined as a TSH outside of the laboratory determined normal range)
4. Desire to continue attempts to conceive for the duration of the program
5. History of bariatric surgery
6. Use of over-the-counter or prescribed weight loss medications with the exception of metformin
7. Enrollment in another clinical trial (excluding surveys)

Primary outcomes:
measure: Term live birth rate
timeFrame: 2.5 years
Secondary outcomes:
measure: Weight loss - goal for weight loss defined as 5 percent of enrollment body weight lost
timeFrame: 6 months
measure: Changes in triglyceride levels
timeFrame: 3 months
measure: Changes in high density lipoprotein levels
timeFrame: 3 months
measure: Changes in alanine aminotransferase (ALT) levels
timeFrame: 3 months
measure: Changes in fasting insulin levels
timeFrame: 3 months
measure: Changes in postprandial insulin levels
timeFrame: 3 months
measure: Changes in fasting glucose levels
timeFrame: 3 months
measure: Changes in postprandial glucose levels
timeFrame: 3 months
measure: Changes in hemoglobin A1c levels
timeFrame: 3 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Ruth Bunker Lathi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Practice Committee of tAmerican Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril. 2008 Nov;90(5 Suppl):S60. doi: 10.1016/j.fertnstert.2008.08.065.
citation: Li TC, Makris M, Tomsu M, Tuckerman E, Laird S. Recurrent miscarriage: aetiology, management and prognosis. Hum Reprod Update. 2002 Sep-Oct;8(5):463-81. doi: 10.1093/humupd/8.5.463.
citation: James PT. Obesity: the worldwide epidemic. Clin Dermatol. 2004 Jul-Aug;22(4):276-80. doi: 10.1016/j.clindermatol.2004.01.010.
citation: Shirazian T, Raghavan S. Obesity and pregnancy: implications and management strategies for providers. Mt Sinai J Med. 2009 Dec;76(6):539-45. doi: 10.1002/msj.20148.
citation: Rich-Edwards JW, Goldman MB, Willett WC, Hunter DJ, Stampfer MJ, Colditz GA, Manson JE. Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol. 1994 Jul;171(1):171-7. doi: 10.1016/0002-9378(94)90465-0.
citation: Jensen MD. Medical management of obesity. Semin Gastrointest Dis. 1998 Oct;9(4):156-62.
citation: Bolumar F, Olsen J, Rebagliato M, Saez-Lloret I, Bisanti L. Body mass index and delayed conception: a European Multicenter Study on Infertility and Subfecundity. Am J Epidemiol. 2000 Jun 1;151(11):1072-9. doi: 10.1093/oxfordjournals.aje.a010150.
citation: van der Steeg JW, Steures P, Eijkemans MJ, Habbema JD, Hompes PG, Burggraaff JM, Oosterhuis GJ, Bossuyt PM, van der Veen F, Mol BW. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod. 2008 Feb;23(2):324-8. doi: 10.1093/humrep/dem371. Epub 2007 Dec 11.
citation: Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008 Sep;90(3):714-26. doi: 10.1016/j.fertnstert.2007.07.1290. Epub 2008 Feb 6.
citation: Lashen H, Fear K, Sturdee DW. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study. Hum Reprod. 2004 Jul;19(7):1644-6. doi: 10.1093/humrep/deh277. Epub 2004 May 13.
citation: Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res. 2002 Jun;10(6):551-4. doi: 10.1038/oby.2002.74.
citation: Metwally M, Saravelos SH, Ledger WL, Li TC. Body mass index and risk of miscarriage in women with recurrent miscarriage. Fertil Steril. 2010 Jun;94(1):290-5. doi: 10.1016/j.fertnstert.2009.03.021. Epub 2009 May 12.
citation: Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod. 1998 Jun;13(6):1502-5. doi: 10.1093/humrep/13.6.1502.